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1 Slide 2 Slide 3 Use of Beta-Blockers In patients With Diabetes Mellitus Professor Taalat Abd El-Aatty Diabetes & Metabolism Alexandria University Slide 4 Questions? 1.Are -blockers contraindicated in diabetes mellitus? 2.Are -blockers still considered as first line treatment of hypertension? 3.Are -blockers the first line treatment for control of hypertension in patients with diabetes? Slide 5 Diabetes mellitus: A Cardiovascular Disease Diabetes alone, without co morbid coronary heart disease (CHD), exposes individuals to the same high risk (>20%) as does prior CHD for a major cardiovascular event (cardiovascular risk equivalent). Diabetes doubles the risk of CVD in men and triples the risk in women. Slide 6 Diabetes mellitus: A Cardiovascular Disease CVD is a major cause of morbidity, mortality for those with diabetes. Common conditions coexisting with T2DM (e.g., hypertension, dyslipidemia) are clear risk factors for CVD. Diabetes itself confers independent risk. Slide 7 Diabetes mellitus & Hypertension twice Hypertension is twice as common in persons with diabetes as it is in the general populations. At age 45, approximately 40% of patients with type 2 diabetes also have hypertension, increasing to 60% by age 75. Slide 8 Diabetes mellitus & Hypertension Truncal obesity, hypertension,, insulin resistance, and dyslipidemia are among the components of the metabolic syndrome, which has been associated with an increased risk of coronary heart disease. Slide 9 "The Goal is to Get to Goal! Hypertension -PLUS- Diabetes or Renal Disease < 140/90 mmHg < 130/80 mmHg In diabetics blood pressure goals are lower, and thus more difficult to achieve. Slide 10 21 % 44 % 56 % Heart Failure Stroke Myocardial infarction UKPDS Slide 11 BETA-BLOCKER Slide 12 Slide 13 Beta 2 on bronchial and vascular smooth muscle - relaxation Increased in heart failure Beta 3 mediate vasodilatation by release of nitric oxide Slide 14 Antihypertensive effect 1.Inhibition of prejunctional beta receptors on the terminal neurons 2.Reduction of central adrenergic outflow 3.Decreased Renin-angiotensin system beta receptors mediate renin release Thus decreases after load and wall stress Slide 15 Slide 16 Slide 17 Slide 18 Slide 19 Beta-Blockers: Side Effects Dizziness, fatigue. Intermittent claudication, Airway obstruction in asthma. Heart block. Raynauds phenomenon. Erectile dysfunction (ED) Hypoglycaemia. Increase in insulin resistance or new-onset diabetes. Slide 20 Slide 21 Slide 22 Slide 23 BB with VD Properties Slide 24 Slide 25 Slide 26 Slide 27 Slide 28 Slide 29 Beta-Blockers: Contraindications Asthma. Atrioventricular block. Diabetes PER SE is Not a Contraindication for use of .blocker Slide 30 Beta-Blockers early Increased insulin resistance and a higher incidence of new-onset diabetes mellitus were reported in early trials with beta-blockers. However, more modern agents such as bisoprolol and carvedilol appear to have no detrimental effect on glucose metabolism. Slide 31 Beta-Blockers not Existing diabetes mellitus is not a contra- indication to beta-blockade, although b1- selective agents are preferable in insulin- dependent patients, to avoid masking hypoglycaemia. Slide 32 Beta-Blockers Patients with diabetes and concomitant CHF or CAD are among those who can benefit most from beta-blockers. European guidelines recommend -blockers for all diabetic patients with acute cardiac syndrome, post-MI, and in CHF. Post-MI beta-blockade reduces mortality by 23% in diabetic patients. In CHF studies, -blockers have consistently shown a significant benefit in patients with diabetes. Slide 33 Meta-analysis by Haas et al. showed that compared with placebo, -blockers for CHF significantly reduces all-cause mortality by 16% in patients with DM. Slide 34 COPERNICUS Study advanced HF equivalently In the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study of carvedilol, in patients with advanced HF, all- cause mortality was reduced equivalently in diabetic and nondiabetic patients. Slide 35 Now back to the 1 st question 1.Are -blockers contraindicated in diabetes mellitus? *-blockers are not contraindicated in patients with diabetes mellitus. *-blockers are highly indicated in diabetics with CAD or CHF. Slide 36 Slide 37 Slide 38 Questions? 1.Are -blockers contraindicated in diabetes mellitus? 2.Are -blockers still considered as first line treatment of hypertension? 3.Are -blockers the first life treatment for control of hypertension in patients with diabetes? Slide 39 JNC 7: -blockers 1 st line anti-hypertensive Compelling Indication* Recommended Drugs DIURETI C BBACEI ARB CCB Aldo ANT Heart failure Post-MI Diabetes Chronic kidney disease Slide 40 NICE/BHS 2006: removed -blockers Slide 41 BMJ 2008; (including LIFE and ASCOT) A meta-analysis favour the use of -blockers -blockers Slide 42 Largest Meta-analysis Conclusions: all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure Conclusions: With the exception of the extra protective effect of blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. BMJ. 2009 May 19 Slide 43 Law et al BMJ 2009 Slide 44 Conclusions of meta-analysis Beta-blockers are vital in treatment of hypertension. its the level of blood pressure reduction that counts. dont trust drug leaflets (and out-dated side-effect warnings). be sensitive and treat macro-economically cost-effectively Slide 45 Recent Guidelines 2009 Slide 46 not ability to reduce BP in hypertension. Large-scale meta-analyses of available data confirm that major antihypertensive drug classes, (diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists, and b-blockers) do not differ significantly for their overall ability to reduce BP in hypertension. Slide 47 no There is also no evidence that major drug classes differ in their ability to protect against overall cardiovascular risk or cause-specific cardiovascular events, such as stroke and myocardial infarction. all initiation Diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists and b-blockers can all be considered suitable for initiation of antihypertensive treatment, as well as for its maintenance. Slide 48 Keeping the number of drug options large increases the chance of BP control in a larger fraction of hypertensives. substantially depends on BP lowering per se, regardless of how it is obtained. Cardiovascular protection by antihypertensive treatment substantially depends on BP lowering per se, regardless of how it is obtained. should be avoided The traditional ranking of drugs into first, second, third and subsequent choice, has now little scientific justification and should be avoided. Slide 49 In the absence of compiling indications Use any anti-hypertensive from the 5 major classes. Slide 50 To answer our 2 nd question 1.Are -blockers contraindicated in diabetes mellitus? 2.Are -blockers still considered as first line treatment of hypertension? *The answer is yes according to large recent meta-analysis and the revised European guidelines in 2009. Slide 51 Questions? 1.Are -blockers contraindicated in diabetes mellitus? 2.Are -blockers still considered as first line treatment of hypertension? 3.Are -blockers the first life treatment for control of hypertension in patients with diabetes? Slide 52 United Kingdom Prospective Diabetes Study (UKPDS) Design: Randomized, controlled trial comparing an ACE inhibitor with a -blocker in preventing complications of type 2 diabetes. Population: 1148 patients with hypertension and type 2 diabetes. Treatment: 758 patients allocated to tight control of BP: nCaptopril (n=400) nAtenolol (n=358) Slide 53 UKPDS Years from Randomization 124 112 257 237 327 314 400 358 Captopril Atenolol No. of patients at risk: Patients With Events (%) 0213546879 Less tight blood pressure control Captopril Atenolol P=0.43 0 10 20 30 40 50 UKPDS Group. BMJ. 1998;317:713-720 Slide 54 UKPDS Conclusion: similar Captopril and atenolol produced similar reductions in BP in hypertensive diabetics. Both drugs were equally effective in reducing risk of: o Fatal and non-fatal diabetic complications o Death related to diabetes o Heart failure o Progression of retinopathy Slide 55 JNC 7: -blockers can be used in diabetics Compelling Indication* Recommended Drugs DIURETI C BB ACEI ARB CCB Aldo ANT Heart failure Post-MI Diabetes Chronic kidney disease Slide 56 ADA Slide 57 2011 ADA Recommendation Level of evidence C Pharmacologic therapy for patients with diabetes and hypertension should include either an ACE inhibitor or ARB. If needed to achieve blood pressure targets, a thiazide diuretic should be added to those with an estimatedGRF 30 mL/min and a loop diuretic for those with an estimated GFR START with ACEI or ARB diuretic) If BP Still Not at Goal (130/80 mm Hg) Add Vasodilator (hydralazine, minoxidil) If BP Still Not at Goal (130/80 mm Hg) If Blood Pressure >130/80 mm Hg in Diabetes + Albuminuria blocker Add CCB or blocker Consider low dose aldosterone antagonists# 2006. American College of Physicians. All Rights Reserved. Slide 60 European Guidelines diabetes protective effect of BP lowering per se. Meta-analyses of available trials show that in diabetes all major antihypertensive drug classes protect against cardiovascular complications, probably because of the protective effect of BP lowering per se. They can thus all be considered for treatment. Slide 61 Questions? 1.Are -blockers contraindicated in diabetes mellitus? 2.Are -blockers still considered