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  • While many of the countries on this list are some of the smallest in the world, they are also experiencing the worst of the epidemic. More than a third of adults in some of these countries have diabetes and the combined toll of complications, deaths, and loss of income make diabetes a real threat not just to the individuals experiencing the disease but also to the economies of the countries themselves.New evidence from Saudi Arabia has put it into the top 10 for the first time and shows the rapid pace of the epidemic in the Middle East and North Africa region. The Western Pacific islands continue to dominate the list where ethnicity combined with changing lifestyles are largely to blame for the high percentages of diabetes.
  • A staggering 50% of people with diabetes do not know they have the disease. Diabetes can go many years without showing symptoms, or symptoms may be misdiagnosed as other conditions, meanwhile high blood glucose is causing damage to major organs in the body. Complications such as cardiovascular disease, neuropathy, retinopathy, and kidney disease are irreversible once they develop and can mean serious disability for the person who experiences them. Regions where the overall prevalence of diabetes is relatively low, such as Africa, have the some of the highest percentages of people who are undiagnosed. This is often because of a complete lack of awareness of the disease both in the public and the health community.

Hfd saudi health specialities part i pharmacists. Hfd saudi health specialities part i pharmacists. Presentation Transcript

  • Agenda – Diabetic Neuropathy. – Diabetic Dyslipidemia
  • The Role Of Community Pharmacists in Managing Patients with Diabetes Many patients with newly diagnosed diabetes are overwhelmed & need information about their disease & medications in a timely or even urgent manner, but some people wait six to eight months to get an appointment at a Diabetes center. Nicole R. Hartnell, Neil J. MacKinnon, Ingrid S. Sketris and David Gass Canadian Pharmacists Journal / Revue des Pharmaciens du Canada 2005 138: 46
  • The Role Of Community Pharmacists in Managing Patients with Diabetes  Community pharmacists could reduce the clinical and economic burden of diabetes by participating in diabetes management .  Pharmacists’ roles in collaboration with other healthcare professionals should be understood before any community pharmacy-based programs focusing on diabetes management are designed and implemented.
  • The Role Of Community Pharmacists in Managing Patients with Diabetes  Patients with diabetes are good candidates for community pharmacy programs, as they see pharmacists five times more often than other healthcare providers.  A variety of healthcare professionals, including physicians, pharmacists, nurses and dieticians agree that diabetic patients can benefit from community pharmacist interventions.  Community pharmacists have an important role to play in patient education, particularly about the management of the disease and the appropriate use of drug therapy.  Consistency of messages and reinforcement of recommendations from other healthcare providers are important facets of pharmacist involvement in any multidisciplinary approach to disease management.
  • Strategies for teaching self-care with type II Diabetes  Diabetes mellitus is a chronic health condition that requires patients to self manage their illness to prevent serious complications. Unfortunately, less than one-half of these patients obtain ideal glycemic control. Studies indicate that educational programs can improve some aspects of control, however the best method for teaching self care is still unknown.  Adult development theory may provide guidance to pharmacists who coach self-care. Developing educational sessions that are tailored to an individual’s learning needs and encouraging problem-solving skills may assist in achieving glycemic control and an optimal quality of life.  Pharmacists are accessible healthcare professionals who liaise with diabetes educators and who can provide long-term support and education to those with diabetes.
  • Macrovascular and Microvascular Complications of Diabetes • Macrovascular disease (coronary artery disease, stroke, transient ischemic attack, cerebrovascular disease, evidence of silent myocardial infarction or ischemia or peripheral arterial disease) • Microvascular disease (especially nephropathy or retinopathy) • Multiple additional risk factors, especially with a family history of premature coronary or cerebrovascular disease in a first-degree relative. • Extreme level of a single risk factor (e.g., LDL-C >5 mmol/L, systolic blood pressure >180 mmHg). • Duration of diabetes >15 years with age >30 years
  • Macrovascular and Microvascular Complications of Diabetes Dyslipidemia  Encourage a healthy lifestyle by recommending smoking cessation, healthy eating habits (Canada’s Food Guide), maintaining a healthy weight and regular physical exercise (moderate intensity 30 to 60 minutes, 4 to 7 days/week).  Educate patients about the benefits of drug therapy and the importance of medication regimen adherence.  Simplify medication regimens with unit-dose packaging, once-daily dosing and fixed-dose combinations where applicable.  Educate patients about potential adverse effects associated with dyslipidemic medications.  Monitor glucose levels in those taking niacin regular and sustained release, as these products can increase blood glucose levels.  Although adverse events associated with lipid-lowering medications are uncommon, monitor for potential medication-related toxicities such as myopathy: muscle aches, weakness without creatinine kinase (CK) rise; myositis: muscle symptoms with ↑ CK levels; rhabdomyolysis (very rare): severe progressive muscle aches, weakness and pain accompanied by large ↑ CK (>10x upper limit of normal) and marked ↑ serum creatinine (yellow-brown urine and myoglobin in the urine) leading to renal failure; hepatotoxicity: ↑ alanine transaminase and aspartate transaminase.
  • Macrovascular and Microvascular Complications of Diabetes • Neuropathy In those with type 2 diabetes, screening for peripheral neuropathy should begin at diagnosis and occur annually. Screening should start after 5 years’ postpubertal duration of type 1 diabetes {Grade D, Consensus}
  • Macrovascular and Microvascular Complications of Diabetes • Diabetic Neuropathy – Emphasize the importance of maintaining optimal blood glucose levels to prevent and delay neuropathy. – Educate patients regarding adverse effects associated with medications used to manage peripheral neuropathy, e.g., antidepressants (dry mouth, blurred vision, drowsiness), anticonvulsants (weight gain, neutropenia, leucopenia) and opioid analgesics (constipation, drowsiness). – Advise patients that damage to the nerves controlling digestion can lead to postprandial nausea, pain, bloating and vomiting. Urinary nerve damage can lead to urinary retention and erectile dysfunction in males. – Educate patients about the signs and symptoms of peripheral neuropathy (pain, pins and needles sensations, burning feeling) that can occur in hands and feet.
  • Macrovascular and Microvascular Complications of Diabetes • Foot Care – Remind patients to have their feet regularly examined by a health professional, and not to self-treat any foot condition (e.g., warts, corns), no matter how minor they may appear. – Educate patients about proper footwear (well-cushioned walking shoes; custom-molded shoes to accommodate bony abnormalities) and to break in shoes slowly and carefully. – Remind patients to check their feet daily (both visually and manually) for signs of skin breakdown (e.g., calluses,erythema, hemorrhage under a callus). Sensory neuropa- thy and loss of feeling can allow trauma to go unnoticed. – Remind patients to avoid foot trauma (never walk barefoot) and to keep feet clean and dry. – Educate patients that all skin conditions including dryness should be treated to prevent more severe conditions.
  • IDF, Diabetes Atlas 2012 update
  • Middle East and North Africa : The Facts • • Country 1. 2. Egypt Iran 3. Saudi Arabia 4. 5. 6. 7. 8. Sudan Algeria Morocco Iraq Syria Cases 7.5 million 4.5 million 3.4 million 1.8 million 1.6 million 1.4 million 1.2 million 898,203 • • • More than 34.2 million people in the MENA Region have diabetes; by 2030 this will rise to 59.7 million Diabetes can lead to serious and costly complications Diabetes caused 356,586 deaths in the MENA Region this year USD 12 billion were spent on treating diabetes in the region The region has the highest prevalence of diabetes in adults (11%) http://www.idf.org/sites/default/files/IDF_MENA_5E_Update_FactSheet.pdf
  • IDF, Diabetes Atlas 2012 update
  • IDF, Diabetes Atlas 2012 update
  • Timeline of Diabetes Mellitus Diagnosis of diabetes Genetic conditional factors Chronic complications Environmental factors ‒ Nutrition ‒ Obesity  Incapacity Sedentary lifestyle IGT Environmental factors ‒ ↓HDL-C Progressive hyperglycemia Hyperglycemia ‒ ↑PPG ↑TG Retinopathy Blind Nephropathy End-point kidney disease Neuropathy Ischemic cardiomyopathy ‒ Atherosclerosis Acute stroke ‒ Hypertension Amputation Ref 37: Brown WV. Diabetes Obes Metab. 2000; 2(suppl 2):S11–S18 17 Death
  • Hyperglycemia Leads to Devastating Long-Term Complications Microvascular Complications Macrovascular Complications Retinopathy Stroke Nephropathy Heart Disease Neuropathy Peripheral Vascular Disease 1% Decrease in A1C = 15% Reduction in Macrovascular and 40% Decrease in Microvascular Complications Source: DCCT and UKPDS
  • The Hidden Complication of Diabetes –Diabetic Peripheral Neuropathy. –Diabetic Dyslipidemia
  • The Hidden Complication of Diabetes – Diabetic Peripheral Neuropathy. – Diabetic Dyslipidemia
  • Diabetic Peripheral Neuropathy • Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, estimated to affect 50% to 90% of patients, depending on the criteria used for diagnosis.1 • Painful diabetic peripheral neuropathy occurs in 65% of people with diabetes in Saudi Arabia2 1. 2. 65.3 % Prevalence of DPN in Saudi Arabia2 TRIPPE B. Diabetic Peripheral Neuropathy: The Forgotten Complication and New Therapeutic Approaches. Review of Endocrinology 2009; Supp:S1-12. Halawa MR, Karawagh A, Zeidan A, et al. Prevalence of painful diabetic peripheral neuropathy among patients suffering from diabetes mellitus in Saudi Arabia. Curr Med Res Opin 2010;26(2):337-43.
  • Painful diabetic peripheral neuropathy is a HIDDEN complication of Diabetes in Saudi. Eligible patients from 100 outpatient clinics treating patients with diabetes mellitus across Saudi Arabia Completed the validated DN4 % Diagnosed Patients Treated Patients 69% 37% 42% 63% On initial evaluation Following evaluation (screening by DN4) 1. Halawa MR, Karawagh A, Zeidan A, et al. Prevalence of painful diabetic peripheral neuropathy among patients suffering from diabetes mellitus in Saudi Arabia. Curr Med Res Opin 2010;26(2):337-43.
  • Main Manifestations of Diabetic peripheral neuropathy (DPN) • Numbness or insensitivity to pain or temperature • Tingling, burning, or prickling sensation • Sharp pains or cramps • • • • 1. Extreme sensitivity to touch, even light touch Loss of balance and co-ordination Muscle weakness and loss of reflexes Burning 68% Symptoms are often worse at night Halawa MR, Karawagh A, Zeidan A, et al. Prevalence of painful diabetic peripheral neuropathy among patients suffering from diabetes mellitus in Saudi Arabia. Curr Med Res Opin 2010;26(2):337-43. National Institute of Diabetes and Digestive and Kidney Diseases. Diabetic Neuropathies: The Nerve Damage of Diabetes. Available at: http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/. Accessed 18 Oct 2011. Tingling or prickling Electric shocks 60% 36%
  • The Patient-Reported Burden of Neuropathic Pain is Significant Reduced quality of life Depression Psychological distress Difficulty in concentration Physical disability Sleep disturbances Both the intensity of the pain and the duration of the condition exacerbate the patient’s burden5 Drowsiness when awake 1. Gilron I et al. CMAJ 2006;175:265-75. 2. Jensen MP et al. Neurology 2007;68:1178-82. 3. Khenioui H et al. Ann Readapt Med Phys 2006;49:125-37. 4. Cruz-Almeida Y et al. J Rehab Res Dev 2005;42:585-94. 5. Meyer-Rosberg K et al. Eur J Pain 2001;5:379-89.
  • Increasing Pain Severity Leads to Increasing Healthcare Utilization in DPN Patients Number of Healthcare Visits 7 6 5 4 3 2 1 0 Mild Moderate Pain Severity (m-BPI-DPN) m-BPI-DPN: modified Brief Pain Inventory - Diabetic Peripheral Neuropathy Severe n = 255
  • Planning the Management of Painful Diabetic peripheral neuropathy (DPN) Treatment Goals Primary >50% pain relief, but be realistic! Do not let "realistic" lead to a less aggressive pursuit of maximum relief • Restoration or improvement in functional measures, quality of life, sleep and mood • Pain and function are modified differently • Treatment should be modifying pain and hopefully improved function will follow • Secondary • If improved function does not follow, take measures to help patients optimize function in the presence of residual pain Argoff CE, et al. Mayo Clin Proc. 2006;81(Suppl 4):S12-25.
  • Treatment for Painful Diabetic Peripheral Neuropathy • Treatment is both preventative and symptomatic, and is based on: – Stabilizing glycemic levels1 – Analgesics specific to neuropathic pain:2 • First-line therapies include alpha-2-delta ligands (pregabalin, gabapentin) and TCAs • Second-line therapies include SNRIs and opioids – Standard NSAIDs are generally ineffective; opioids may be useful in certain cases3 TCAs = tricyclic antidepressants; SNRIs = serotonin-norepinephrine reuptake inhibitors; NSAIDs = non-steroidal anti-inflammatory drugs 1. Corbett CF. Diabetes Educ 2005;31:523-38. 2. Bohlega S et al. J Int Med Res 2010;38:101-23. 3. Dray A. Br J Anaesth 2008;101:48-58.
  • Non-pharmacologic Treatment for Neuropathic Pain • Given their presumed safety, nonpharmacologic treatments should be considered whenever appropriate1 • In general, non-pharmacologic treatment is complementary to drug therapy2 • Non-pharmacologic treatment options for chronic pain in general include2: – – – – Physiotherapy Pain management programs Acupuncture TENS TENS = transcutaneous electrical nerve stimulation 1. Gilron I et al. CMAJ 2006;175:265-75. 2. IASP. Pain Clinical Updates 2010;17:1-6.
  • International Guidelines Recommending Pregabalin as First-line for Peripheral Neuropathic Pain GuidelineP First-line recommendations Second-line recommendations Middle East Region1 Pregabalin, gabapentin, TCAs, lidocaine (topical)¶ SNRIs (duloxetine or venlafaxine-XR), opioid analgesics (e.g., tramadol, oxycodone) French-speaking Maghreb2 Pregabalin, gabapentin, TCAs, lidocaine (topical) SNRIs (venlafaxine-XR or duloxetine), tramadol South Africa Pregabalin, amitriptyline EFNS3 Pregabalin, gabapentin, TCAs, duloxetine, venlafaxine ER, lidocaine (topical) Tramadol, opioids, capsaicin (patches) IASP*4 Pregabalin, gabapentin, TCAs, duloxetine, venlafaxine, lidocaine (topical) Opioid analgesics, tramadol CPS*5 Pregabalin, TCAs, gabapentin SNRIs, lidocaine (topical) AAN**6 Pregabalin† Gabapentin, duloxetine, venlafaxine, sodium valproate, amitriptyline, tramadol, oxycodone, capsaicin‡ ¶For focal neuropathy, such as post-herpetic neuropathy; *No differentiation between different types of neuropathic pain; **For painful diabetic peripheral neuropathy only †Population based on at least 2 consistent Class I studies (RCTs); Level B: probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population based on at least one Class l study (RCT) 7 EFNS = European Federation of Neurological Societies; IASP = International Association for the Study of Pain; CPS = Canadian Pain Society; AAN = American Academy of Neurology; TCAs = tricyclic antidepressants; SNRIs = serotonin-norepinephrine reuptake inhibitors; RCT = randomized controlled trial. 1. Bohlega S et al. J Int Med Res 2010;38:101-23. 2. Griene B et al. Douleur analg 2011;24:112-20. 3. Attal N et al. Eur J Neurol 2010;17:1113-e88. 4. Dworkin RH et al. Mayo Clin Proc 2010;85(3 Suppl):S3-14. 5. Moulin DE et al. Pain Res Manag 2007;12:13-21. 6. Bril V. et al. Neurology 2011;76:1-8. 7. AAN Classification of Recommendations. Available at: http://www.neurology.org/site/misc/NeurologyFiller.pdf. Accessed: 1 Nov 2011.
  • AAN Evidence-Based Treatment Guidelines for DPN1 (2011) Summary of recommendations: 1. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76:1-1.
  • AAN Evidence-Based Treatment Guidelines for DPN1 (2011) Pregabalin is the only level A treatment for Diabetic Painful Neuropathy Level A: established as effective, ineffective, or harmful (or as useful/predictive or not useful/not predictive) for the given condition in the specified population based on at least 2 consistent Class I studies (RCTs) 2 Level B: probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population based on at least one Class l study (RCT)2 AAN = American Academy of Neurology; DPN = diabetic peripheral neuropathy; RCT = randomized controlled trial 1. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76:1-1.
  • Pregabalin: efficacy in patients with painful diabetic peripheral neuropathy Placebo (n=550) Pregabalin 150 mg/day (n=175) Pregabalin 300 mg/day (n=265) Pregabalin 600 mg/day (n=507) Endpoint least-squares mean change in pain scores 0 -0.5 -1 -1.5 -1.49 -2 -2.05* -2.5 -3 -2.36† *p=0.007 vs. placebo †p<0.0001 vs. placebo -2.75† Pregabalin significantly reduces pain associated with painful diabetic peripheral neuropathy Pain reductions are positively correlated with dosage Freeman R et al. Diabetes Care 2008;31:1448-54.
  • Pregabalin in neuropathic pain – real-life clinical practice: efficacy Pain intensity at baseline and during treatment with pregabalin 10 Pain intensity at baseline and during treatment with pregabalin, ordered by etiology of the polyneuropathy 10 8 Pain intensity* Pain intensity* 8 6 -62% 4 2 0 6 4 2 0 1 2 3 Week 4 5 6 *Intensity of neuropathic pain was recorded on an 11-point numeric rating scale (0 = no pain, 10 = maximum imaginable pain). Mallison R et al. MMW Fortschr Med 2007;149:S13-20. 0 1 2 3 4 5 Week 0 6 7 1. Diabetic polyneuropathy (n=5,091) 2. Post-herpetic neuralgia (n=2,187) 3. Trigeminal neuralgia (n=1,548) 4. Polyneuropathy with malignant tumor (n=406) 1 2 3 4 5 Week 6 6 7 5. Alcoholic polyneuropathy (n=803) 6. Polyneuropathy of the other etiology (n=2,379) 7. Back pain with neuropathic component (n=4,271)
  • Reduction in pain and pain-related sleep interference with pregabalin in peripheral neuropathic pain Pain-related sleep interference Pain Pregabalin dose (mg/day) 150 (n=425) 300 (n=495) 600 (n=582) -1 -2 * * * -3 0 Mean chnage from baseline Mean chnage from baseline 0 Placebo (n=828) Pregabalin dose (mg/day) Baseline mean score ~6.6 150 (n=425) 300 (n=495) 600 (n=582) -1 -2 * * * -3 *p<0.001 vs. placebo -4 Placebo (n=827) *p<0.001 vs. placebo -4 Baseline mean score ~5.1 Seventer RV, et al. Profile of sleep effects of pregabalin in patients with chronic pain syndromes and in healthy volunteers. Presented at: EFIC; Istanbul, Turkey; 2006.
  • Pregabalin: effect on the components of the triad of pain Pain Sleep Anxiety -43.1%* -42.3%* Percent reduction in mean score 0 -5 -10 -15 -20 -25 -30 -35 -40 -39.7%* -45 -50 *p<0.0001 vs. baseline Adapted from Baron R et al. Eur J Pain 2008;12:850-58.
  • The Hidden Complication of Diabetes –Diabetic Neuropathy. – Diabetic Dyslipidemia
  • High Incidence of Dyslipidemia in the Diabetic Population 100% <100 Men >40 <150 Women >50 Patients with diabetes (%)* 80% 60% 100-129 150-199 40% Men 40 130 20% Women 50 200 0% Men Women LDL-C (mg/dL) *245 men with diabetes and 253 women with diabetes aged 18 years from NHANES 1999-2000. Men Women Triglycerides (mg/dL) Men Women HDL-C (mg/dL) Ref 9: Modified from Jacobs MJ et al. Diabetes Res Clin Pract. 2005;70:263-269.
  • CVD—Most Common Cause of Death in People With Diabetes Approximately 65% of patients with diabetes will die of cardiovascular or cerebrovascular disease 45 40 Percent death (%) 35 30 25 20 15 10 5 0 Ischemic heart disease Other heart disease Diabetes Cancer Ref 5: Geiss LS et al. In: National Diabetes Data Group, ed. Diabetes in America. Washington, DC: NIH; 1995. Publication 95-1468. 38 Stroke Pneumonia / Influenza Other
  • In the UKPDS, Among CHD Risk Factors, LDL-C Ranked As the Strongest Predictor of CHD Risk in Patients With Diabetes Stepwise selection of risk factors, adjusted for age and sex, in 2693 white patients with diabetes, with dependent variable as time to first CHD event Risk factor P-value† First LDL-C <0.0001 Second HDL-C 0.0001 Third HbA1c 0.0022 Position of significance for CHD event Fourth Systolic BP 0.0065 Fifth Smoking 0.056 For every 39 mg/dL increase in LDL-C, the risk of CHD increased by nearly 60% *United Kingdom Prospective Diabetes Study. †P 39 Ref 42: Turner RC et al. BMJ. 1998;316:823-828. values are significance of risk factor after accounting for all other risk factors in model.
  • Lipid Treatment Guidelines in Patients With Diabetes (NCEP Guidelines) Guidelines Lipid targets in diabetes patients Treatment recommendations NCEP ATP III 2004 Update Patients without CVD LDL-C <100 mg/dL Institution of LDLlowering drugs along with dietary therapy when LDL-C levels are ≥130 mg/dL in patients with diabetes Patients with CVD Optional LDL-C goal: <70 mg/dL Ref 11A: Grundy SM et al. Circulation. 2004;110:227-239. 40 Intensive lipid-lowering therapy with a statin in patients with diabetes and CVD, regardless of baseline LDL-C levels
  • According to the ESC/EAS Guidelines • Patients with diabetes should aim to achieve LDL-C <70 mg/dL (1.8 mmol/L) and/or a 50% LDL-C reduction when the target cannot be reached • The CTT meta-analysis further indicates that subjects with type 2 diabetes will benefit from cholesterollowering therapy in RRR to a similar degree as nondiabetic patients, but being at higher absolute risk the absolute benefit will be greater resulting in a lower NNT. Ref 13: ESC/EAS Guidelines for the management of dyslipidemias European Heart Journal (2011) 32, 1769–1818. 41
  • Primary Prevention of CVD with Statins in Patients with Diabetes CARDS
  • CARDS Study Design: Collaborative Atorvastatin Diabetes Study Patient Population • Collaboration in the UK with BDA and NHS • Type 2 diabetics • No prior MI or CHD • LDL-C <160 mg/dL Atorvastatin 10 mg Primary End Point • 43 Time to first occurrence of major CV event (CHD death, nonfatal MI, stroke, revascularization) 2838 Patients Double-blind Placebo 4 years Ref 14 A: Colhoun HM, et al. for the CARDS Investigators. Lancet. 2004;364:685-696. Ref 14 B: CARDS design paper. Diabet. Mesd 2002: 19:201 - 211
  • CARDS: Major CV Events* Atorvastatin 10 mg Cumulative Incidence (%) Number of events: 83 Placebo 15 Number of events: 127 37% Risk Reduction 10 5 HR = 0.63 (95% CI, 0.48–0.83) P=0.001 0 0 1 2 3 4 4.75 Years * Primary end point: acute coronary heart disease events (myocardial infarction including silent infarction, unstable angina, acute coronary heart disease death, resuscitated cardiac arrest), coronary revascularization procedures, or stroke. Ref 14 A: Colhoun HM, et al. for the CARDS Investigators. Lancet. 2004;364:685-696. 44
  • CARDS: Treatment Effect on the Primary End Point Event Event rate, n (%) Hazard ratio (95% CI) RRR Placebo Atorvastatin Primary end point 127 (9.0%) 83 (5.8%) 37% P=0.001 Acute coronary events 77 (5.5%) 51 (3.6%) 36% Coronary revascularization 34 (2.4%) 24 (1.7%) 31% Stroke 39 (2.8%) 21 (1.5%) 48% 0.2 0.4 Atorvastatin better Ref 14 A : Colhoun HM et al. Lancet. 2004;364:685-696. 45 0.6 0.8 1.0 1.2 1.4 Placebo better
  • Secondary Prevention of CVD in Patients with Diabetes – Atorvastatin TNT – Diabetes
  • TNT Study Design: Patients With Diabetes Patient population: • Age: 35-75 years • CHD • LDL-C: 130-250 mg/dL (3.4-6.5 mmol/L) • Triglycerides: 600 mg/dL (6.8 mmol/L) Primary end point: • Time to occurrence of a major CV event: – CHD death – Nonfatal, non–procedure-related MI – Resuscitated cardiac arrest – Fatal or nonfatal stroke Baseline Screening Open-label run-in Double-blind period and wash-out n=1501 LDL-C: <130 mg/dL (<3.4 mmol/L) 1-8 weeks 8 weeks Ref 18: Shepherd J et al. Diabetes Care. 2006;29:1220-1226. 47 n=753 Atorvastatin 10 mg LDL-C target: 100 mg/dL (2.6 mmol/L) n=748 Atorvastatin 10 mg Atorvastatin 80 mg LDL-C target: 75 mg/dL (1.9 mmol/L) Median follow-up = 4.9 years
  • TNT: Time to First Major Cardiovascular Event* in Patients With Diabetes 135 events 20 Cumulative incidence of events (% of patients) Atorvastatin 10 mg (n=753) Atorvastatin 80 mg (n=748) 15 103 events 25% relative risk reduction 10 5 Hazard ratio = 0.75 (95% CI 0.58, 0.97) P = 0.026 0 0 1 2 3 Time (years) *CHD death, nonfatal non–procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke. Ref 18: Shepherd J et al. Diabetes Care. 2006;29:1220-1226. 48 4 5 6
  • Hazard Ratios in Patients With and without Diabetes: Secondary Efficacy Outcomes Event rate (diabetes) 10 mg 80 mg Major CV event 17.9% Event rate (non-diabetics) 10 mg 80 mg 13.8% 9.7% All-cause mortality 8.9% 9.8% 4.8% 39.8% 10.6% 29.3% 7.0% 7.2% 9.1% 10.8% 0.4 0.6 Atorvastatin 80 mg better * The black lines showing the CI are for the subjects who had no diabetes Ref 18: Shepherd J et al. Diabetes Care. 2006;29:1220-1226. 49 4.9% 4.9% PAD 8.2% 1.6% 5.1% CHF with hosp. 10.0% 3.4% 2.4% Cerebrovascular 32.0% 20.2% 4.2% Any coronary 12.9% 6.0% 25.5% Major coronary 44.1% 26.1% 7.5% Any CV event 7.8% 31.6% * 0.8 1.0 1.2 1.4 1.6 Atorvastatin 10 mg better
  • Additional Atorvastatin Studies in Patients with Diabetic Nephropathy
  • TNT Study Design: Treatment Assignment by Diabetes and CKD Status Open-label run-in Atorvastatin 10 mg Double-blind period Patients randomized (n=9656*) No diabetes (n=8225*) Diabetes (n=1431*) CKD (eGFR <60 mL/min/1.73 m2) (n=546) Atorvastatin 10 mg (n=273) Atorvastatin 80 mg (n=273) Normal eGFR† (eGFR ≥60 mL/min/1.73 m2) (n=885) Atorvastatin 10 mg (n=441) *Only patients with complete renal data (baseline and ≥1 post-baseline serum creatinine measurement) were included †Includes normal and mild renal impairment (Stage 2) patients Ref 32: Shepard J, et al. Mayo Clin Proc. 2008;83(8):870-879 51 Atorvastatin 80 mg (n=444)
  • Time to First Major CV Event by Baseline Diabetes and CKD Status 20 HR = 1.32 (95% CI 1.00, 1.72) P=0.049 Event rate 17.4% Diabetic patients % of patients with major CV event* CKD (n=546) Normal eGFR (n=885) 15 Event rate 13.4% Nondiabetic patients CKD (n=2561) Normal eGFR (n=5664) Event rate 10.0% 10 Event rate 7.8% 5 HR = 1.30 (95% CI 1.12, 1.52) P=0.0007 *CHD death, nonfatal non–procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke 0 0 1 2 3 4 Time (years) Ref 32: Shepard J, et al. Mayo Clin Proc. 2008;83:870-879 52 5 6
  • Time to First Major CV Event by Treatment in Patients With Diabetes and CKD 30 Atorvastatin 10 mg (n=273) % of patients with major CV event* Atorvastatin 80 mg (n=273) 25 HR = 0.65 (95% CI 0.43, 0.98) P=0.037 20 15 10 Relative risk reduction = 35% 5 0 *CHD death, nonfatal non–procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke 0 1 2 3 4 Time (years) Ref 32: Shepard J, et al. Mayo Clin Proc. 2008;83:870-879 53 5 6
  • Time to First Major CV Event by Treatment in Patients With Diabetes and Normal eGFR % of patients with major CV event* 30 Atorvastatin 10 mg (n=441) Atorvastatin 80 mg (n=444) 25 HR = 0.90 (95% CI 0.63, 1.29) P=0.56 20 15 10 Relative risk reduction = 10% 5 *CHD death, nonfatal non–procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke 0 0 1 2 3 4 Time (years) Ref 32: Shepard J, et al. Mayo Clin Proc. 2008;83:870-879 54 5 6
  • ADA Summary of Recommendations for Adults With Diabetes (2012) Glycemic and BP Control Lipids  A1C <7%  Preprandial glucose 70-130 mg/dl  LDL<100 mg/dl (<2.6 mmol/l)  Peak postprandial glucose <180 mg/dl  BP<130/80 mmHg  <70mg/dl (< 1.8mmol/l) with CVD  TGs <150 mg/dl (<1.7 mmol/l)  HDL>50 mg/dl (>1.1 mmol/l) Neuropathy screening and treatment • All patients should be screened for distal symmetric polyneuropathy (DPN) starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes and at least annually thereafter, using simple clinical tests • Medications for the relief of specific symptoms related to painful DPN and autonomic neuropathy are recommended, as they improve the quality of life of the patient