23. Classification and Management of BP for adults *Treatment determined by highest BP category. † Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. JNC 7 slideset Two-drug combination for most † (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Yes or > 100 > 160 Stage 2 Hypertension Drug(s) for the compelling indications. ‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Yes or 90–99 140–159 Stage 1 Hypertension Drug(s) for compelling indications. ‡ No antihypertensive drug indicated. Yes or 80–89 120–139 Prehypertension Encourage and <80 <120 Normal With compelling indications Without compelling indication Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification
24. Sudden Deaths by Time of Day Peckova et al. Circulation 1998;98:31
26. The Reasons Why Low-Dose Diuretics Should be Initial Therapy 1. They reduce cardiovascular morbidity and mortality. 2. They lower blood pressure, particularly in patients consuming excessive sodium. 3. They enhance the antihypertensive efficacy of all other antihypertensive drugs. 4. They rarely cause side effects. 5. They reduce calcium loss and osteoporosis. 6. They are relatively inexpensive.
29. CV Events in Swedish Trial in Old Persons (Stop-2) Conventional Rx (diuretics and B-blockers) compared to ACE-Is and CCBs No difference in BP outcomes No overall difference in EVENTS Lancet 1999;354:751
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32. Heart Outcomes Preventions Evaluation (HOPE) Study Events ACE-1 (Ramipril)* Regimen that did not include an ACE-1 No. Randomized 4645 4652 % Reduction in Risk - Ramipril:Other therapy MI, Stroke, CVD 22 CV death 25 MI 20 Stroke 31 Non-CV death +3 (NS) All cause mortality 16 *10 mg/day - 62.5% remained on Rx at 4.5 years New Engl J Med 11/10/99
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34. En pacientes de alto riesgo (HOPE, IRMA, IDNT, RENAAL, and LIFE), el uso de un IECA (o un ARA) usualmente con un diuretico) reducen eventos CV mas que un regimen que no incluye estas medicaciones.
36. Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril Years to CHD Event 0 1 2 3 4 5 6 7 Cumulative CHD Event Rate 0 .04 .08 .12 .16 .2 0.81 0.99 (0.91-1.08) L / C 0.65 0.98 (0.90-1.07) A / C p value RR (95% CI)
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41. Benefits of Lowering BP by Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50% -12 -4-5 About mmHg
No significant difference was observed between amlodipine (the red line) and chlorthalidone (the blue line) for the primary outcome. The relative risk for amlodipine compared to chlorthalidone was 0.98, with a 95% confidence interval of 0.90-1.07. Also, no significant difference was observed between lisinopril (the green line) and chlorthalidone for the primary outcome. The relative risk was 0.99, with a 95% confidence interval of 0.91-1.08.
The three core messages for the ALLHAT antihypertensive trial are: Diuretics should be the drug of choice for first step therapy of hypertension For the patient who cannot take a diuretic (which should be an unusual circumstance), CCB’s and ACEI’s may be considered. Most hypertensive patients require more than one drug. Diuretics should generally be part of the antihypertensive regimen. Lifestyle advice should also be provided.
Combination therapy reduced blood pressure by 12/5 mm Hg and reduced stroke risk by 43% - the benefit was similar in hypertensive patients as well as normotensives. By contrast, single-drug therapy reduced blood pressure by 5/3 mm Hg with no statistically significant reduction in stroke risk, although the confidence interval is wide a risk reduction of up to 23% for stroke cannot be ruled out. It is important to remember that patients were randomized between active agent and placebo - active agent could have been single or combination therapy as determined by the patients physician. Therefore, the study was powered to detect reductions in stroke risk in the active treatment group. There was not a sufficient patient base receiving single agent to detect a statistically significant risk reduction in stroke.