Great Expectations
From telomeres to TECOS, causes for celebration and despair

Cover Story | London In Great Expectations, Charles Dickens wrote, “Take nothing on its looks; take everything on evidence. There’s no better rule.” That’s why we go to scientific sessions. He also wrote, “There was a long hard time when I kept far from me the remembrance of what I had thrown away when I was quite ignorant of its worth.” The current value of some old approaches–and a reminder of the basics–also were front and center at this year’s meeting of the European Society of Cardiology (ESC). And, of course, there were a number of encouraging trials, albeit tempered with clear evidence that cutting-edge medicine just can’t keep up with our deteriorating lifestyles. After ESC, there is reason for both celebration and despair.

Move It or Lose It

Whether we experience them or not, we all know the many benefits of regular physical activity and now we have interesting insights into why it’s so good for us. The reason goes well beyond the cardiovascular system and lands right at the telomeres, the caps at the end of each strand of DNA that protect our chromosomes.

At the ESC meeting, investigators showed that a combination of physical activity and cognitive training reduces mild cognitive impairment (MCI) and, when you train the brain, leukocyte telomere length (LTL) is increased. In one telomere study presented at ESC.15, 94 individuals with MCI were compared to 37 age- and sex-matched controls. Fifty patients with MCI were randomly placed in a 3-hour environmental enrichment therapy program 3 times a week for 7 months, participating in tailored, stepwise physical, cognitive, and social training. A no-training group of 27 patients received standard treatment. Leukocyte telomere length was evaluated by real-time polymerase chain reaction (PCR) before and after 7-month intervention period.

Patients with MCI and controls had a similar prevalence of traditional cardiovascular risk factors. The relative telomere length (T/S) ratio was significantly reduced in the MCI group compared with controls (p = 0.02). After a 7-month follow-up period, patients in the training group showed a significantly increased LTL when compared to baseline (0.97 ± 0.21 vs. 1.03 ± 0.23; p = 0.03). An opposite trend was observed in the no-training group.

In a second study, investigators found an inverse relationship between LTL and risk of coronary artery stenosis (CAS). They studied 254 patients with a confirmed diagnosis of CAS who were matched 1:1 on age and sex with a group of controls without CAS. For each 1 SD shorter LTL, patients experienced a 54% higher risk of CAS (odds ratio: 1.54; 95% confidence interval [CI]: 1.15-2.06; p = 0.0037). After adjusting for cardiovascular risk factors, individuals in the shortest LTL tertile had 2.57 times (p = 0.007) higher CAS risk compared to subjects in the longest LTL tertile.

(A third study demonstrated that telomere length predicts clinical outcomes following revascularization procedures, suggesting this could be a novel marker for systemic oxidative stress and cardiovascular aging.)

Sanjay Sharma, MD, is professor of inherited cardiac diseases and sports cardiology at St. George’s University of London, England. In a highlights program offering the “Best of ESC” broadcast soon after the meeting, he said, “Exercise and other healthy lifestyle measures do preserve telomere length and people who exercise modestly have a telomere length about 10% greater than sedentary individuals and looks the same size as someone who is 6 years younger. That may explain why exercise gives us another 3 to 6 years of life.”

Aspiring, but Failing

The goal of the European survey known as EUROASPIRE was to measure modifiable risk factors, describe their current management, and improve lifestyle trends. Unfortunately, it did not work out that way.

In 1994, the ESC and others published joint prevention guidelines and patients with coronary heart disease (CHD) were deemed a priority for secondary prevention. The first survey was conducted in nine countries in 1995-96, followed by EUROASPIRE II in 15 countries (1999-2002), EUROASPIRE III (2006-07) in 22 countries, and EUROASPIRE IV in 14 countries (2012-13). All of these were carried out in centers offering interventional cardiology and cardiac surgery. More recently, a primary care arm of EUROASPIRE IV was conducted (2014-15).

Data from the first two surveys demonstrated a high prevalence of unhealthy lifestyles, modifiable risk factors, and insufficient use of pharmacotherapy to reduce high blood pressure, lipid levels, and blood glucose. Also alarming was increased smoking, particularly among younger patients, and swelling levels of obesity across all centers. Despite greater understanding of the familial ties that bind in heart disease, EUROASPIRE II found that only one in 10 first-degree relatives of patients with premature CHD were being evaluated for their own cardiovascular risk. Finally, wide variations in preventive practices were seen among centers. A recipe ripe for change­—or disaster.

Kornelia Kotseva, MD, PhD, a senior clinical research fellow at the National Heart and Lung Institute, Imperial College, London, analyzed the time trends. Of 12,775 participating patients, 8,456 were interviewed: 3,320 in EUROASPIRE II, 2,632 in EUROASPIRE III, and 2,513 in EUROASPIRE IV. (Study interviews took place ≥ 6 months but ≤ 3 years after the recruitment interview.) Some of the data (covering the five countries participating in all the surveys) were presented at ESC with a broader swath of cumulative data published in the October 6, 2015, issue of JACC.1 (Scan the QR code to watch our CSWN interview with Dr. Kotseva.)

The findings produced little encouragement that things were moving in the right direction:

  • Smoking prevalence has stayed the same (17% to 20%) but the proportion of people with no intention of quitting has risen in the last 7 years (34% today). Use of pharmacotherapy for smoking cessation remains very low, meaning more emphasis is needed in this area.
  • Obesity (32%, 33%, 39%, for EUROASPIRE II, III, and IV respectively; p = 0.007) and self-reported diabetes (19%, 24%, 27%; p = 0.004) both increased.
  • Therapeutic control of blood pressure in patients using blood pressure-lowering medication slightly improved but not significantly (28% and 35%; p = 0.12), with 65% of patients above the recommended target in EUROASPIRE IV.
  • The proportion of patients on lipid-lowering medication who met the low-density lipoprotein (LDL) cholesterol target increased insignificantly­—yet 63% of patients still did not reach the target. Glycemic control in patients with diabetes remained unchanged (62% and 60%; p = 0.75), with 40% of patients not achieving the target of glycosylated hemoglobin (HbA1c) < 7% in EUROASPIRE IV.
  • Use of cardioprotective drugs increased between surveys II and III, but there was no significant change between surveys III and IV.

According to professor David Wood, MD, also of the Imperial College London: “We seem to have hit a ceiling on the use of cardioprotective medications. Most patients use optimal drug treatment but do not benefit fully because of their poor lifestyle.”

He added that management of blood pressure and lipids has improved, “but again the benefits are mitigated by poor lifestyle and a growth in obesity and diabetes. Our analysis highlights the pressing need for modern preventive cardiology programs with lifestyle change at their core and not simply writing prescriptions for drugs.”

Dr. Keith A. A. Fox, MB, ChB, FACC, professor at the University of Edinburgh and co-moderator of the “Best of ESC” program, commented on the trial, saying, “We learned from Euroaspire that we are very ineffective in dealing with most of the patients we should be treating for both primary and secondary prevention. We really need to do better to do with what we already have in hand.”

Dr. Sharma agreed: “People come to this [ESC] meeting to learn how to manage cardiovascular disease, but the results of Euroaspire were disappointing. We really need to focus hard on preventing cardiovascular disease.”

Extended DAPT:

Yes? No? Maybe?

The authors of the OPTIDUAL trial suggest that extending dual antiplatelet therapy (DAPT) beyond the recommended 12 months after coronary stenting “should be considered” in patients at low risk for bleeding. In reporting the results, news stories on the trial ranged from “Results suggest extending post-stenting DAPT beyond 1 year” to “No clear need to lengthen DAPT” to “No harm, no foul with DAPT after 4 years.”

Not exactly black and white.

Here’s what the trial showed: In 1,385 patients from 58 French sites, a combination of aspirin and clopidogrel did not decrease the rate of major adverse cardiovascular and cerebrovascular events (MACCE; see FIGURE 1), but there was “a hint” it might reduce ischemic outcomes without excess bleeding.2

Specifically, OPTIDUAL showed a borderline reduction in ischemic outcomes (a post-hoc outcome composite rate of death, myocardial infarction [MI], or stroke) with extended DAPT (4.2% in the extended-DAPT group and 6.4% in the aspirin group; hazard ratio: 0.64, 95% CI: 0.40-1.02; p = 0.06) without increased bleeding (2.0% in both groups) or increased all-cause mortality.

According to principal investigator Gérard Helft, MD, PhD, from the Institut de Cardiologie, Hôpital Pitié-Salpétrière, in Paris, France, “Given the lack of harm and the signal for benefit of prolonged DAPT in the OPTIDUAL trial, and the results from prior randomized trials testing long durations of DAPT, prolongation of DAPT beyond 12 months should be considered in patients without high-risk bleeding, who have received a drug-eluting coronary stent and are event-free at 12 months.”

In a press conference, Dr. Helft acknowledged that determining the optimal approach for any given patient is “difficult.” Better risk stratification is certainly needed. That means more use of CHA2DS2-VASc score (which calculates stroke risk for patients with atrial fibrillation [AF]) and the bleeding risk score known as HAS-BLED.

Marco Roffi, MD, a professor at University Hospital of Geneva, Switzerland, noted during the live “Best of ESC” program that while OPTIDUAL was underpowered, the intimation of benefit goes in the same direction as a meta-analysis presented at the meeting, suggesting that prolonged DAPT was associated with a 22% relative risk reduction in MACCE, corresponding to an absolute 1.1% risk reduction in events and a number needed to treat of 90. “This has to be weighed against the increased risk of major bleeding in the same meta-analysis,” said Dr. Roffi. “So, I think, the guidelines are correct and you have to assess risk of ischemic events and risk of bleeding and then decide on a case-by-case fashion. But for the first time, the (new ESC) guidelines open the way for prolonged dual antiplatelet therapy in patients at high ischemic risk and low bleeding risk.”

Specifically, while the general recommendation of DAPT for 1 year remains, new ESC guidelines for managing patients with acute coronary syndrome (ACS) who require percutaneous coronary intervention state that a tailored duration (i.e., shortened to 3-6 months or extended up to 30 months) is now allowed in selected patients at high-bleeding or high-ischemic risk, respectively.1 Professor Roffi acknowledged that balancing risk with benefit is “not easy.” He stressed, “If you have a patient with acute myocardial infarction undergoing stenting, then reassess the patient at 12 months. At this time, use the criteria of the PEGASUS study, which determined risk based on the presence of diabetes, multivessel disease, renal insufficiency, maybe the patient has already had multiple events; if they have such risk factors, then maybe consider prolonged (DAPT) if they remained free of bleeding events.”

Doesn’t That Just Blow?

The SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) study showed that this particular ventilatory support therapy effectively treats central sleep apnea, which is found in 25% to 40% of patients with heart failure. Unfortunately­—well, here is Martin R. Cowie, MD, the study’s first author: “There was no difference in outcome and, surprisingly­—which has taken cardiologists and respiratory physicians completely by surprise—we found an increase in mortality. And, if you look at cardiovascular mortality, it was up 34% (TABLE 1). So, not only does it not make any difference to patients with systolic HF, it actually increases the risk of them dying. This is a real game-changer trial, really important.”

Of course, obstructive sleep apnea responds well to positive airway pressure (PAP), but for central sleep apnea, which is a neurological problem that can spring from many different causes, a different kind of device was thought to be necessary. The adaptive servo-ventilation machine uses an algorithm that detects significant reductions or pauses in breathing and intervenes with just enough support to maintain the patient’s breathing at 90% of what had been normal prior to decreased breathing. In this approach, the pressure being delivered to the patient is not as important as the amount of air that the patient is receiving.

What the heck happened? For a full blow-by-blow, you can read the paper, which was simultaneously published in the New England Journal of Medicine.3 The authors lay out two main possibilities. First, maybe PAP in general—not specifically adaptive servo-ventilation—might lead to adverse consequences on cardiac function in some patients, such as those with HF, particularly those with atrial fibrillation or low pulmonary-capillary wedge pressures who have reductions in cardiac output when PAP is applied. A second possibility is that some aspects of Cheyne–Stokes respiration may be beneficial. Thus, the elimination of Cheyne–Stokes respiration (by, let’s say, adaptive servo-ventilation) may remove an important compensatory mechanism.

In an accompanying editorial,4 Ulysses J. Magalang, MD, and Allan I. Pack, MB, ChB, PhD, suggest, “Until other studies clarify whether the results seen in the SERVE-HF trial are a consequence of the specific device that was used, we recommend that adaptive servo-ventilation not be used outside clinical trials in patients with heart failure who have predominantly central sleep apnea.”

Likewise, the potentially deleterious effect of PAP therapy is also relevant to the many patients with HF who have predominantly obstructive sleep apnea because, at present, therapy with continuous PAP is still recommended for these patients. However, as Drs. Magalang and Pack noted in their editorial, since the clinical approach to patients with predominantly central events is now quite different from the approach to patients with predominantly obstructive events, “it is essential that patients are well studied, with appropriate measurements to distinguish obstructive from central events. Moreover, adjustment of continuous PAP in these patients with predominantly obstructive events must take place in the sleep laboratory, since the reliability of the algorithms in current auto-adjust machines to determine the various types of sleep-disordered breathing events in these patients is unknown.”

Good-as-Gold Drugs that are ‘Cheap as Chips’

In patients with resistant hypertension despite triple therapy, adding spironolactone is significantly more effective than adding other blood pressure-lowering drugs, according to results of the PATHWAY-2 trial. According to Bryan Williams, MD, a professor at University College London, “It is remarkable that after 50 years we have not seen trials comparing different drugs for treating resistant hypertension. We tested spironolactone because small studies suggested this might be a good drug. It came out on top; it was by far the best drug controlling blood pressure in the most patients and even at the end of the study there was almost no one not controlled or at least almost controlled with these drugs.”

In 314 patients, spironolactone lowered systolic blood pressure 8.70 mm Hg versus placebo

(p < 0.001), about twice that achieved with doxazosin (-4.03 mm Hg) and bisoprolol (-4.48 mm Hg) (TABLE 2). Both agents led to significantly greater reductions compared to placebo

(p < 0.001 for both). Overall, almost three quarters of patients with uncontrolled blood pressure saw a major improvement in their blood pressure on spironolactone, with almost 60% meeting a stringent measure of blood pressure control (p < 0.001). Bisoprolol and doxazosin where the best drug in only 17% and 18% of patients respectively.

Dr. Williams said spironolactone (25-50 mg daily) is “overwhelmingly the most effective drug treatment for resistant hypertension.” He added, “Maybe the definition [of resistant hypertension] needs to be revisited, because now we know spironolactone is so effective in many of these patients it should be defined as resistant to the three drugs we have used before PLUS spironolactone.” Indeed, in presenting his data, Dr. Williams concluded that patients should not be defined as having resistant hypertension unless their blood pressure remains uncontrolled on spironolactone

The drug works so well, he said, “Based on the criteria used for renal denervation, we would have had a total of only 15 patients who would qualify.”

In the live program, “Best of ESC,” Dr. Sharma noted, “What grabbed me the most is that these are old drugs changing paradigms with an excellent outcome. These [drugs] are as cheap as chips; this is important in the current financial climate. I am concerned about the impact on ethnicity, because it is the black population who is more likely to have resistant hypertension and impaired glucose tolerance. In Africa and South America where there are limited resources, these drugs could be revolutionary.” Added Dr. Fox, “These are generic therapies that could be added to standard of care with widespread applicability and that is an important take-home from this Congress.”

Situation Improves for Sitagliptin

It has been the worst of times for a number of diabetes drugs. Cardiologists found reason for caution after evidence that some new agents to treat diabetes may be associated with increased CV risk that could wipe out any gains from better glycemic control. It was at the 2014 ESC meeting, for example, where Dr. Sharma emphasized that good glycemic control benefits microvascular disease but not macrovascular disease. Consequently, he said, “We need to ease off on the ‘sweet spot’ for glycated hemoglobin and focus more on other risk factors for atherosclerosis because in high-risk individuals, there is evidence long-acting insulins have precipitated MI and now the glitazones and gliptins have been associated with heart failure.”

For example, SAVOR-TIMI 53 (the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trial was a large international clinical trial that randomized patients to a selective dipeptidyl peptidase 4 (DPP-4) inhibitor or placebo. According to John J.V. McMurray, MD, FACC, a professor at the University of Glasgow, “The results suggested that the drug might increase the risk of heart failure (and) heart failure is the most diabetagenic diseases there is; anywhere between 30% and 50% of heart failure patients have diagnosed or undiagnosed diabetes.” We need new treatments, but those safety concerns were a major stumbling block. However, Dr. McMurray says, with new data, things look better now.

At ESC.15, investigators presented further pre-specified analysis of the larger study called TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin). The initial TECOS findings, presented earlier this year at the American Diabetes Association, were adjusted to control for baseline heart failure and the results left some unanswered questions. (Such as, so what is the effect of the drug on HF?) Darren McGuire, MD, MHSC, FACC, first author of the study, from the University of Texas Southwestern Medical Center, Dallas, TX, told the media, “Now we present unadjusted analyses [also pre-specified] with identical results, and we complement these with mulitivariable analyses—all yielding the identical conclusion: no signal of any sort for heart failure risk with sitagliptin (TABLE 3). No matter how we sliced and diced the data, the same result was observed.”

A second trial presented at ESC also may calm some frayed nerves in the industry. This study looked at a glucagon-like peptide-1 (GLP-1) for reducing HbA1c in people with type 2 diabetes and recent ACS. Lixisenatide did not increase or decrease the rate of CV events compared to placebo, according to the results of ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome). Lixisenatide also seemed safe in patients with a history of heart failure, with similar hazard ratios for active therapy and placebo. However, among the patients who were hospitalized for HF during follow-up, the risk of all-cause death was nine-fold greater than those who were not hospitalized for heart failure.

After the latest data were presented, Dr. Sharma noted that TECOS was a noninferiority trial, but he remained optimistic: “We still should not be punching our arms in the air over this but although glycemic control has a modest effect on the heart, it has a very significant effect on microvascular effects. And the fact that we now can use another oral hypoglycemic effect to prevent microvascular complications—like retinopathy, remember blindness due to diabetes is the most common cause of blindness today—is a very big deal.”

One piece of bad news: while many people were on their way to the ESC meeting, the U.S. Food and Drug Administration (FDA) added a new warning to the label for “the gliptins”—sitagliptin, saxagliptin, linagliptin, and alogliptin. In a statement, the FDA said the medications “may cause joint pain that can be severe and disabling,” and the agency “has added a new Warning and Precaution about this risk to the labels of all medicines in this drug class.” (The FDA release is here:

OK, let’s end this discussion of diabetes drugs on a high note. As this issue of CSWN was going to press, results were announced for a major trial evaluating empagliflozin, a selective inhibitor of sodium glucose cotransporter 2 that has been approved for type 2 diabetes. The drug significantly reduced the risk of the combined endpoint of CV death, non-fatal heart attack, or non-fatal stroke by 14% when added to standard of care in patients with type 2 diabetes at high risk of CV events.5 Over a median of 3.1 years, there was a 38% reduction in CV death, with no significant difference in the risk of non-fatal MI or non-fatal stroke.

Our former editor-in-chief of CardioSource WorldNews, Christopher P. Cannon, MD, FACC, of Brigham and Women’s Hospital, who was not involved in the study, said, “The EMPA-REG OUTCOME trial results are encouraging for health care professionals and their patients. Patients in the study were already being treated with medications that have been proven to reduce cardiovascular events. The observation that empagliflozin provided additional cardiovascular death reduction on top of these other medications is a very important finding.”

Depression: The Strongest Predictor of Angina

Patients with depression, whether women or men, are three times more likely to experience more frequent chest pain than those without depression. This was found to be true in patients with and without obstructive coronary artery disease.

The study included 5,825 adults enrolled in the Emory Cardiovascular Biobank. Importantly, reducing the severity of depression symptoms was associated with a decrease in the frequency of chest pain at follow-up. However, patients with depression who underwent revascularization did not have an improvement in chest pain frequency at 1-year follow-up.

Registry Updates
These were “registries” highlighted at ESC.


Patients with atrial fibrillation who receive antithrombotic management according to ESC guidelines have better outcomes than those who do not, according to 1-year follow up results from the ESC’s EURObservational Research Programme Pilot survey on Atrial Fibrillation (EORP-AF Pilot) General Registry.6

“This is the first study to show better outcomes using the 2012 ESC guidelines on atrial fibrillation,” said principal investigator Professor Gregory Y.H. Lip, MD, FACC, from the University of Birmingham, United Kingdom, and Aalborg University, Denmark. “This is novel as the 2012 guidelines—for the first time—focused on the initial identification of ‘low-risk’ patients (that is, CHA2DS2-VASc score 0 in men, 1 in women) who did not need any antithrombotic therapy, following which oral anticoagulation can be offered to those with one or more stroke risk factors. Older guidelines had a categorical approach to stroke risk stratification and treatment decisions were more focused on identifying ‘high-risk’ patients to be targeted for oral anticoagulation treatment but many patients were suboptimally untreated.”


The EORP has another pilot registry; this one for Chronic Ischemic Cardiovascular Disease (EORP-CICD). Investigators evaluated changes in the use of life-saving medications over the past 10 years and found an increased rate of such prescriptions. At discharge from hospital, 93% of patients received a statin (up from 48%), 65% received an angiotensin-converting enzyme inhibitor (ACE I) (up from 40%), and 80% received a beta-blocker (up from 67%).

“The increase in medications is a good sign,” said Michel Komajda, MD, FACC, a professor at University Pierre and Marie Curie and Pitié-Salpêtrière Hospital in Paris, France. “However, the proportion of patients who are taking all recommended medications at the same time remains suboptimal at 71% (ACE I/angiotensin receptor blocker, statin, and aspirin), so there is room for improvement.”


Preoperative statins are associated with a 17% reduction in cardiac complications (the primary endpoint; p = 0.007) and a 43% reduction in all-cause mortality (p = 0.004) after noncardiac surgery, according to results from the VISION (Vascular events In noncardiac Surgery patIents cOhort evaluatioN) Study. A total of 15,478 patients aged 45 years and older undergoing noncardiac surgery were recruited from 12 centers in eight countries. To make “comparable” groups, they did propensity score matching, leaving 2,845 patients (18.4%) treated with a statin and 4,492 patients (29.0%) who did not receive a statin.

P.J. Devereaux, MD, PhD, McMaster University, Hamilton, Ontario, Canada, chair of the VISION Steering Committee, said: “Among the 200 million adults worldwide who undergo noncardiac surgery annually, more than 10 million will suffer a cardiovascular complication in the first 30 days after surgery. Despite the magnitude of the problem, no intervention has been shown to be both safe and effective in the prevention of cardiovascular complications such as heart attack, death due to cardiac causes, and stroke.” However, the VISION results suggest that statins have the potential to prevent cardiovascular complications in patients undergoing noncardiac surgery.


At ESC, investigators reported on major bleeding in an assessment of 6,784 patients with atrial fibrillation treated with rivaroxaban for stroke prevention.7 XANTUS is the first international, prospective real-world non-vitamin K antagonist oral anticoagulant (NOAC) study in patients with AF. In a report simultaneously published, mean patient age was 71.5 years, 41% were female, and 9.4% had documented severe or moderate renal impairment (creatinine clearance <50 ml/min). The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4, respectively; 859 (12.7%) patients had a CHA2DS2-VASc score of 0 or 1. The mean treatment duration was 329 days. The rate of fatal bleeding was 0.2% per year, while stroke occurred in 0.7% patients per year, and 0.4% of patients per year experienced an intracranial hemorrhage. Compare that to the patients in the pivotal ROCKET AF trial who had a mean CHADS2 score of 3.5, and the incidence of major bleeding in those taking rivaroxaban was 3.6 per 100 person-years.

“These results demonstrate low rates of both major bleeding and stroke in patients taking rivaroxaban in routine clinical practice,” said

A. John Camm, MD, FACC, professor of clinical cardiology at St. George’s University of London. He added that XANTUS showed that the majority of patients (80%) persisted on rivaroxaban treatment throughout the 1-year study period, whereas other recent data on vitamin K antagonists have shown a persistence rate of 62% after 1 year. “Treatment persistence is especially important as discontinuation of anticoagulation leaves patients with AF unprotected from the risk of stroke,” said Professor Camm.

Please see the nearby link to our CSWN interview with study co-author W. Frank Peacock, IV, MD, a professor of emergency medicine at Baylor College of Medicine and the associate chief of emergency medicine research there.


Final data from ODYSSEY familial hyperglycemia (FH) I and II studies represent the single largest collection of patients with heterozygous familial hypercholesterolaemia (HeFH) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy. In on-treatment analyses, the recently approved PCSK9 inhibitor, alirocumab, reduced mean LDL-C levels to < 2.2 mmol/l (85 mg/dl) at weeks 24–78 of treatment. These are levels hitherto unobtainable with maximum doses of statin, even with the addition of other lipid-lowering therapies, in patients with HeFH.

The incidence of adverse events was generally similar between alirocumab and control group patients. Adverse events resulted in discontinuation in 3.4% of alirocumab-treated patients in ODYSSEY I (vs. 6.1% placebo) and 3.6% (vs. 1.2%) in ODYSSEY II.8

Late this summer, alirocumab, from Regeneron Pharmaceuticals Inc. and Sanofi SA, was the second PCSK9 inhibitor to be approved in about a month (the first being evolocumab from Amgen). Alirocumab was approved by the U.S. FDA for use in addition to diet and maximally-tolerated statin therapy in adult patients with HeFH or patients with clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Scan the QR code to watch our CSWN interview with Professor Michel Farnier MD, PhD, Point Medical, Dijon, France, and senior author of the study.


  1. Kotseva K, De Bacquer D, Jennings C, et al. J Am Coll Cardiol. 2015;66:(14):1636-7.
  2. Helft G, Steg PG, Le Feuvre C, et al. Eur Heart J. 2015 Sep 12. [Epub ahead of print]
  3. Cowie MR, Woehrle H, Wegscheider K, et al. N Engl J Med. 2015;373:1095-105.
  4. Magalang UJ, Pack AI. N Engl J Med. 2015;373:1166-7.
  5. Zinman B(1), Wanner C, Lachin JM, et al. N Engl J Med. 2015 Sep 17. [Epub ahead of print]
  6. Lip GYH, Laroche C, Popescu MI, et al. Europace. 2015 [Epub ahead of print]
  7. Camm AJ, Amarenco P, Haas S, et al. Eur Heart J. 2015 Sep 1. [Epub ahead of print]
  8. Kastelein JJ, Ginsberg HN, Langslet G, et al. Eur Heart J. 2015 Sep 1. [Epub ahead of print]

Clinical Topics: Prevention, Stress

Keywords: Aging, Cardiovascular Diseases, Cardiovascular System, Cognition, Confidence Intervals, Coronary Stenosis, DNA, Leukocytes, Cognitive Dysfunction, Motor Activity, Oxidative Stress, Real-Time Polymerase Chain Reaction, Risk, Risk Factors, Telomere, CardioSource WorldNews

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