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Circadian variation in cardiovascular events among diabetics in the convince trial
AJH–May 2004 –VOL. 17, NO. 5, PART 2
POSTERS: Clinical Trials
P-390 COMBINATION OF LOSARTAN AND HYDROCHLOROTHIAZIDE IN NON-DIPPERS HYPERTENSIVE PATIENTS Maria J Armas-Hernandez, Rosalba Cammarata, Beatriz SosaCanache, Maria C Armas-Padilla, Beatriz Pacheco, Jaime Guerrero, Rafael Hernandez-Hernandez. Clinical Pharmacology Unit, Hypertension Clinic, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Lara, Venezuela. The aim of this study was to evaluate the combination of 100 mg of losartan plus 25 mg of hydrochlorothiazide (HCTZ) on a group of twelve moderate to severe untreated non-dipper hypertensive patients. Patients (6 each sex, age: 52.2 ⫾ 2.2 years) were untreated for at lease four weeks and classify as non-dipper by ambulatory blood pressure monitoring (ABPM). They received treatment daily at 08:00 ⫾ 1 hour during six weeks. ABPM was carried out during the last day of placebo and active treatment in a single blind fashion. For ABPM analysis daytime was considered from 06:30 to 22:30 and night-time from 22:31 to 06:29. Results in mean values ⫾ SE are shown as follows: Losartan-HCTZ combination Placebo (ⴙ/ⴚSE) (ⴙ/ⴚSE) % Change Day-time SBP (mmHg) Day-time DBP (mmHg) Night-time SBP (mmHg) Night-time DBP (mmHg) 24 h Heart Rate (bpm)
152.7⫹/⫺1.9 99.2 ⫹/⫺1.6 153.4⫹/⫺5.3 97.5⫹/⫺3.25
135.0⫹/⫺1.6* 88.2⫹/⫺1.5* 136.1⫹/⫺5.7** 87.6⫹/⫺3.6**
⫺14.4⫹/⫺3.6 ⫺14.5⫹/⫺0.9 ⫺13.9⫹/⫺3.6 ⫺12.7⫹/⫺3.3
74.3⫹/⫺1.8
77.9⫹/⫺2.2
⫹4.7⫹/⫺1.1
* p ⱕ 0.001; ** p ⱕ 0.04
In conclusion, combination of losartan - HCTZ reduced blood pressure in non-dipper hypertensive patients, reductions were higher during daytime.
177A
derived from this model can be used to “adjust” (in a single step) analyses comparing outcomes between atenolol and HCTZ.
Characteristic
# of Patients
OR
95% CI
Hispanics Prior MI Prior BP Meds Dyslipidemia Prior CVD Men LVH SBP (10 mm Hg) Age (per year) Diabetes Obesity Blacks
582 655 6926 2591 1629 3669 1026 Avg ⫽ 150 Avg ⫽ 66 1632 4121 568
2.25 1.86 1.61 1.30 1.29 1.27 1.22 1.04 0.98 0.88 0.88 0.68
1.82–2.81 1.55–2.23 1.41–1.83 1.17–1.44 1.14–1.46 1.15–1.40 1.06–1.40 1.01–1.07 0.97–0.99 0.78–0.99 0.79–0.97 0.56–0.82
Key Words: Atenolol, Hydrochlorothiazide, Propensity Score
P-392 CIRCADIAN VARIATION IN CARDIOVASCULAR EVENTS AMONG DIABETICS IN THE CONVINCE TRIAL Henry R Black, William J Elliott, Gregory Grandits, Patricia Grambsch, James D Neaton, William B White, Robert J Anders. Department of Preventive Medicine, RUSH Medical College, Chicago, IL; Division of Biostatistics, University of Minnesota, Minneapolis, MN; Clinical Pharmacology and Hypertension, University of Connecticut, Farmington, CT; Clinical Research, Pharmacia Corporation, Skokie, IL.
Key Words: Losartan, Hydrochlorothyazide, Non-Dipper
P-391 FACTORS IN THE CHOICE OF BETA-BLOCKER VS. DIURETIC FOR INITIAL TREATMENT OF HYPERTENSION IN CONVINCE Henry R Black, William J Elliott, Gregory Grandits, Patricia Grambsch, James D Neaton, Peter Sleight, William B White, Alberto Zanchetti, Robert J Anders. Department of Preventive Medicine, RUSH Medical College, Chicago, IL; Division of Biostatistics, University of Minnesota, Minneapolis, MN; Cardiovascular Medicine, Oxford University, Oxford, United Kingdom; Clinical Pharmacology and Hypertension, University of Connecticut, Farmington, CT; Institute of Physiology and Hypertension, University of Milan, Milano, Italy; Clinical Research, Pharmacia Corporation, Skokie, IL. The benefits of an initial beta-blocker for hypertension in individuals over age 60 are controversial. In the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial, 16,476 hypertensive patients were randomized to verapamil or the physician’s choice of atenolol or hydrochlorothiazide (HCTZ), and followed for 3 years. To investigate which baseline characteristics may have influenced the physician’s selection of atenolol vs. HCTZ as the control treatment, a multiple logistic regression analysis was performed. The “# of patients” in the table below is the number for whom atenolol was selected by the investigator. Significant predictors (and their Odds Ratios [ORs], atenolol vs. HCTZ) included: Factors associated with choosing atenolol or HCTZ were generally consistent with current guidelines. Propensity scores © 2004 by the American Journal of Hypertension, Ltd. Published by Elsevier Inc.
Myocardial infarction, sudden cardiac death and stroke all occur more commonly in the morning (6 AM to noon). Diabetic hypertensives have a 2-4 fold higher absolute risk for cardiovascular events, compared to non-diabetics, but often have blunted or reversed circadian variations in pulse rate, blood pressure, and plasma cortisol levels. To compare diabetics and non-diabetics regarding the circadian pattern of cardiovascular events, we examined data from the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial, in which the time of day for cardiovascular events was prospectively recorded.
Time of Day
Diabetics
Non-Diabetics
12:01 AM-6 AM 6:01 AM to Noon 12:01 PM to 6 PM 6:01 PM to Midnight
29 (18%) 52 (33%) 40 (25%) 39 (24%)
77 (20%) 134 (35%) 90 (23%) 87 (22%)
After an average of 3 years of follow-up, there were 729 first strokes, myocardial infarctions or cardiovascular deaths; 217 occurred in 3239 diabetics, and 160 of these had the time of day recorded. The distribution of times of events between diabetics and non-diabetics was not significantly different (P ⫽ 0.88, chi-square, 3 df). These observations may be confounded by small numbers and poor adherence to initial treatment, but probably not by the initial randomized treatment group. These data suggest that, in CONVINCE, diabetics and non-diabetic hypertensive patients displayed a similar circadian pattern of cardiovascular events. Key Words: Chronobiology, Cardiovascular Events, Epidemiology 0895-7061/04/$30.00
POSTERS: Clinical Trials
P-390 COMBINATION OF LOSARTAN AND HYDROCHLOROTHIAZIDE IN NON-DIPPERS HYPERTENSIVE PATIENTS Maria J Armas-Hernandez, Rosalba Cammarata, Beatriz SosaCanache, Maria C Armas-Padilla, Beatriz Pacheco, Jaime Guerrero, Rafael Hernandez-Hernandez. Clinical Pharmacology Unit, Hypertension Clinic, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Lara, Venezuela. The aim of this study was to evaluate the combination of 100 mg of losartan plus 25 mg of hydrochlorothiazide (HCTZ) on a group of twelve moderate to severe untreated non-dipper hypertensive patients. Patients (6 each sex, age: 52.2 ⫾ 2.2 years) were untreated for at lease four weeks and classify as non-dipper by ambulatory blood pressure monitoring (ABPM). They received treatment daily at 08:00 ⫾ 1 hour during six weeks. ABPM was carried out during the last day of placebo and active treatment in a single blind fashion. For ABPM analysis daytime was considered from 06:30 to 22:30 and night-time from 22:31 to 06:29. Results in mean values ⫾ SE are shown as follows: Losartan-HCTZ combination Placebo (ⴙ/ⴚSE) (ⴙ/ⴚSE) % Change Day-time SBP (mmHg) Day-time DBP (mmHg) Night-time SBP (mmHg) Night-time DBP (mmHg) 24 h Heart Rate (bpm)
152.7⫹/⫺1.9 99.2 ⫹/⫺1.6 153.4⫹/⫺5.3 97.5⫹/⫺3.25
135.0⫹/⫺1.6* 88.2⫹/⫺1.5* 136.1⫹/⫺5.7** 87.6⫹/⫺3.6**
⫺14.4⫹/⫺3.6 ⫺14.5⫹/⫺0.9 ⫺13.9⫹/⫺3.6 ⫺12.7⫹/⫺3.3
74.3⫹/⫺1.8
77.9⫹/⫺2.2
⫹4.7⫹/⫺1.1
* p ⱕ 0.001; ** p ⱕ 0.04
In conclusion, combination of losartan - HCTZ reduced blood pressure in non-dipper hypertensive patients, reductions were higher during daytime.
177A
derived from this model can be used to “adjust” (in a single step) analyses comparing outcomes between atenolol and HCTZ.
Characteristic
# of Patients
OR
95% CI
Hispanics Prior MI Prior BP Meds Dyslipidemia Prior CVD Men LVH SBP (10 mm Hg) Age (per year) Diabetes Obesity Blacks
582 655 6926 2591 1629 3669 1026 Avg ⫽ 150 Avg ⫽ 66 1632 4121 568
2.25 1.86 1.61 1.30 1.29 1.27 1.22 1.04 0.98 0.88 0.88 0.68
1.82–2.81 1.55–2.23 1.41–1.83 1.17–1.44 1.14–1.46 1.15–1.40 1.06–1.40 1.01–1.07 0.97–0.99 0.78–0.99 0.79–0.97 0.56–0.82
Key Words: Atenolol, Hydrochlorothiazide, Propensity Score
P-392 CIRCADIAN VARIATION IN CARDIOVASCULAR EVENTS AMONG DIABETICS IN THE CONVINCE TRIAL Henry R Black, William J Elliott, Gregory Grandits, Patricia Grambsch, James D Neaton, William B White, Robert J Anders. Department of Preventive Medicine, RUSH Medical College, Chicago, IL; Division of Biostatistics, University of Minnesota, Minneapolis, MN; Clinical Pharmacology and Hypertension, University of Connecticut, Farmington, CT; Clinical Research, Pharmacia Corporation, Skokie, IL.
Key Words: Losartan, Hydrochlorothyazide, Non-Dipper
P-391 FACTORS IN THE CHOICE OF BETA-BLOCKER VS. DIURETIC FOR INITIAL TREATMENT OF HYPERTENSION IN CONVINCE Henry R Black, William J Elliott, Gregory Grandits, Patricia Grambsch, James D Neaton, Peter Sleight, William B White, Alberto Zanchetti, Robert J Anders. Department of Preventive Medicine, RUSH Medical College, Chicago, IL; Division of Biostatistics, University of Minnesota, Minneapolis, MN; Cardiovascular Medicine, Oxford University, Oxford, United Kingdom; Clinical Pharmacology and Hypertension, University of Connecticut, Farmington, CT; Institute of Physiology and Hypertension, University of Milan, Milano, Italy; Clinical Research, Pharmacia Corporation, Skokie, IL. The benefits of an initial beta-blocker for hypertension in individuals over age 60 are controversial. In the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial, 16,476 hypertensive patients were randomized to verapamil or the physician’s choice of atenolol or hydrochlorothiazide (HCTZ), and followed for 3 years. To investigate which baseline characteristics may have influenced the physician’s selection of atenolol vs. HCTZ as the control treatment, a multiple logistic regression analysis was performed. The “# of patients” in the table below is the number for whom atenolol was selected by the investigator. Significant predictors (and their Odds Ratios [ORs], atenolol vs. HCTZ) included: Factors associated with choosing atenolol or HCTZ were generally consistent with current guidelines. Propensity scores © 2004 by the American Journal of Hypertension, Ltd. Published by Elsevier Inc.
Myocardial infarction, sudden cardiac death and stroke all occur more commonly in the morning (6 AM to noon). Diabetic hypertensives have a 2-4 fold higher absolute risk for cardiovascular events, compared to non-diabetics, but often have blunted or reversed circadian variations in pulse rate, blood pressure, and plasma cortisol levels. To compare diabetics and non-diabetics regarding the circadian pattern of cardiovascular events, we examined data from the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial, in which the time of day for cardiovascular events was prospectively recorded.
Time of Day
Diabetics
Non-Diabetics
12:01 AM-6 AM 6:01 AM to Noon 12:01 PM to 6 PM 6:01 PM to Midnight
29 (18%) 52 (33%) 40 (25%) 39 (24%)
77 (20%) 134 (35%) 90 (23%) 87 (22%)
After an average of 3 years of follow-up, there were 729 first strokes, myocardial infarctions or cardiovascular deaths; 217 occurred in 3239 diabetics, and 160 of these had the time of day recorded. The distribution of times of events between diabetics and non-diabetics was not significantly different (P ⫽ 0.88, chi-square, 3 df). These observations may be confounded by small numbers and poor adherence to initial treatment, but probably not by the initial randomized treatment group. These data suggest that, in CONVINCE, diabetics and non-diabetic hypertensive patients displayed a similar circadian pattern of cardiovascular events. Key Words: Chronobiology, Cardiovascular Events, Epidemiology 0895-7061/04/$30.00