Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Canadian Society of Internal Medicine 2011

Halifax, Nova Scotia / October 12-15, 2011

Written by Corey Toal, PhD; Chief Medical Editor: Léna Coïc, MD, Montréal, Quebec

Managing the patient with multiple cardiovascular (CV) risk factors often involves lifestyle changes including diet modification, smoking cessation and implementation of an exercise routine. However, a change in lifestyle alone is often insufficient to modulate risk. Therefore, the focus of this report will be on sessions at this year’s CSIM that dealt with managing CV risk.

Managing CV Risk in the Patient with Renal Disease

Dr. Findlay McAlister, University of Alberta, Edmonton, started the session by providing some encouraging data indicating that from a random sample of 6000 Canadian adults, the average systolic blood pressure (BP) in males is 124 mm Hg and 118 mm Hg in females, perhaps reflecting the care provided by primary care physicians. The most recent data show that approximately 65% of Canadian hypertensive patients are treated and controlled compared to the US where the comparable value is 50%. However, in a recent article by Leiter et al. (Can J Cardiol 2011;27(2):e1-e33), emerging cardiometabolic risk factors and their combinations, including fasting blood glucose, lipids, BP, obesity and renal disease, all need to be better managed. Dr. Sheldon Tobe, University of Toronto, Ontario, indicated that national surveys suggest some 4.3% of individuals have glomerular filtration rates (GFR) <60 mL/min/ 1.73 m² which is suggestive of chronic kidney disease (CKD). Go et al. (N Engl J Med 2004;351(13):1296-305) demonstrated that as estimated GFR (eGFR) declined from >60 mL/min/1.73 m² to <15 mL/min/1.73 m², there was a progressive increase in hospitalization, CV events and death. Dr. Tobe told delegates, “Proteinuria is the most significant factor for progression to CKD, actually more potent than the stage of GFR,” and both declining GFR and proteinuria are markers of increased CV risk. “The lower achieved albuminuria leads to better renal outcomes, but once you get below 1 g/day, therapy targeted at only lowering proteinuria is not going to provide that much further benefit, so focus should shift to lowering global CV risk,” he suggested.

One approach to further modifying the CV risk in CKD patients is to better manage their lipids. However, in patients with more severe kidney disease, hemodialysis or a transplant, studies such as 4D (Wanner et al. N Engl J Med 2005;353:238-48), ALERT (Holdaas et al. Lancet 2003;361:2024-31) and AURORA (Fellstrom et al. N Engl J Med 2009;360:1395-407) showed no benefit with the addition of statins. Previous studies on statins in patients with coronary artery disease and other CV risk profiles have demonstrated benefit.

The Study of Heart and Renal Protection (SHARP; Baigent et al. Lancet 2011;377:2181-92) (N=9438) was designed to determine the impact of LDL-C on major atherosclerotic events (coronary death, myocardial infarction [MI], non-hemorrhagic stroke or any revascularization) in patients with CKD; however, two-thirds of the patients were not yet on dialysis, 80% of these had albuminuria and a median eGFR 27 mL/min/1.73 m². In those patients randomized to a combination of ezetimibe 10 mg/simvastatin 20 mg, after almost 5 years of treatment follow-up in the overall group, there was a significant decrease in mean LDL-C of 32 mg/dL (0.83 mmol/L). This resulted in a relative risk reduction of 17% (P=0.002) compared to placebo-treated patients. With further analysis of the dialysis and non-dialysis patient subgroups at randomization, it appeared that the greatest derived benefit was in the non-dialysis patients with approximately a 25% risk reduction in this group.

In order to optimally manage the overall CV risk in patients with CKD, Dr. Tobe suggested the following strategy: lower BP to target (<130/90 mm Hg) using renin-angiotensin-aldosterone system (RAAS) blockade; in all patients with CKD, use a primary prevention strategy for LDL-C reduction using a low-dose statin (e.g. simvastatin 10-20 mg/day) with the addition of ezetimibe for greater LDL-C reduction without the need for higher statin doses; and manage diabetes and institute lifestyle modifications overall.

Acute Coronary Syndrome

In assessing the patient with acute coronary syndrome (ACS), Dr. Iqbal Bata, Dalhousie University, Halifax, Nova Scotia, emphasized the need for rapid (within the first 10 minutes of patient contact) 12-lead resting ECG. He noted, “The ECG will give you prognostic information because depending on the ECG, you can predict the event rate and you need to know how to manage that patient.” He suggested that ST-elevation MI (STEMI) patients show more occlusive disease than non-STEMI (NSTEMI) or unstable angina (UA) patients.

Dr. Michael Love, Dalhousie University, discussed the recent guidelines and standard of care for treating the patient with ACS. He indicated that in the Canadian context, data from the Nova Scotia Cardiovascular Health database capture every patient presenting to the hospital with ACS over the last decade and show that CV all-cause mortality is most frequent in patients presenting with NSTEMI (22%) relative to patients with STEMI (17%) or UA (8%). He emphasized how the real-world clinical setting is different from clinical trials. Moreover, he suggested, “Patients with NSTEMI are usually older, sicker with more complex coronary artery disease, other more complex vascular disease and other more complex medical problems.” Dr. Love indicated that the ACS realities are that NSTEMI ACS outnumbers STEMI by three- to fourfold, and that the majority (70%) of patients are medically managed and not sent for coronary artery bypass grafting or percutaneous coronary intervention. He stated, “Antiplatelet therapy is a key to the medical management of these patients.” He reminded his colleagues that the Canadian Cardiovascular Society guidelines refer to the outpatient management of the patient with ACS, not how to manage the patient acutely. In addition, as part of the working group, Dr. Love noted that dual antiplatelet therapy combination of ASA and a P2Y₁₂ inhibitor should be used in the majority of ACS patients not at high risk of bleeding.

Dr. Bata also emphasized the advantage of “dual antiplatelet therapy to block multiple pathways for activation.” In contrast to medical management, Dr. Bata indicated that if a patient with high risk (recurrent pain, heart failure, pulmonary edema, electrical instability, troponin rise) has an NSTEMI, they could benefit significantly from an invasive strategy.

Atrial Fibrillation

In an overview of the guidelines for treating patients with atrial fibrillation (Afib), Dr. Jafna Cox, Dalhousie University, and Dr. Timothy Pollak, University of Calgary, Alberta, emphasized the rationale of using the CHADS2 score to evaluate the risk of patients presenting with Afib. They noted that the causes of Afib can be of cardiac origin (e.g. hypertension, valvular heart disease, left ventricular dysfunction, etc.) or non-cardiac (e.g. obesity, hyperthyroidism, obstructive sleep apnea, etc.). The CHADS2 score is also a useful tool for directing treatment strategies to prevent stroke in patients with Afib. It was noted that the European Society of Cardiology was now using the CHADS2-VASC risk tool since it considered vascular disease, age between 65 and 74 and women as additional risk factors in the overall risk calculation.

Dr. Pollak indicated, “Patients need to be assessed individually for the benefit/risk of using anticoagulants since bleeding is inevitable with these agents, but considerable benefit can also be derived with some of the newer agents (e.g. direct thrombin inhibitors or factor Xa inhibitors).” He added that from a practice perspective (physician and patient), the newer agents offer considerable ease of use over warfarin.

Diabetes

There are now 370 million people worldwide with diabetes, noted Dr. Bernard Zinman, University of Toronto. Compared to people without diabetes, diabetic patients have higher mortality rates by about 4 to 10 times in people of 20 to 44 years and 2 to 3 times higher in people aged 45 to 79 years. Dr. Zinman advocated a different approach from the usual stepwise paradigm to treating patients with diabetes, in that a proactive approach of starting early with diet and oral combination therapy right from the start results in better control of HbA1c. The genesis of this approach derives from the work of Shah et al. (Diabetes Care 2005;28:600-6) who showed a clinical inertia in response to inadequate glycemic control of diabetic patients of 45% among specialists and 37% among primary care physicians.

For new therapies to treat diabetes, Dr. Zinman indicated that compounds that work through the incretin system show characteristics closest to the ideal for treatment. GLP-1 mimetics and GLP-1 analogues have been shown to decrease HbA_1c (0.8%) and weight (2.5 kg) significantly after 30 weeks for the former and decrease HbA_1c (1.5%), weight (7.5 kg in 25% of patients) and even BP of 3.5 mm Hg with the later agents.

Dr. Zinman suggested, “Any diabetes drug that is proven to have a CV benefit—that is, reducing the risk of CV disease—will obviously go to the top of the list and likely be used very early on in the treatment of diabetes.”

Summary

Patients with ACS, Afib, diabetes and CKD often present with multiple risk factors. Optimal patient care requires treatment strategies that quantify the risk of each factor and institute therapy to manage that risk, employing evidence-based guideline approaches where possible. In certain diseases, combination therapies should be initiated early in the treatment plan. Newer treatments in diabetes which more closely influence physiologic responses (i.e. incretin modulators) can lead to potential benefit in overall diabetes risk management. Combination therapy for lipid management has been shown to reduce atherosclerotic events in patients with CKD with most benefit derived if started early in the disease.