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Association of BP control and frequency of mortality and CV morbidity in hypertensive patients with CAD: the international verapamil SR-trandolapril study
116A
POSTERS: Antihypertensive Drugs
Methods: This randomized, double-blind, placebo-controlled crossover study was performed in 18 non-smokers with Stage I hypertension (10 pts w/o ASCVD [Group A; 60% males; 50% whites]; 8 pts w/ASCVD [Group B; 63% males; 50% white]). Nine pts had hyperlipidemia (8 treated with statins). Patients received IRB or placebo for 6 weeks each (the IRB dose was uptitrated from 150 mg to 300 mg after 3 wks), with a 4-wk wash-out. No antiplatelet, or antidepressant agents, or NSAID were permitted. PAGG was tested with thrombin-receptor agonist (TRA) and adenosin-diphosphate (ADP). Plasma concentration of CRP, IL-6, P-and E-selectins were obtained at baseline and at the end of each treatment period. Results: IRB treatment decreased SBP (mean ⫾ SD mm Hg; from 146.4 ⫾ 12.4 to 140.7 ⫾ 10.3; p⬍0.05). There was a greater impact of IRB on reduction of ADP-induced PAGG in Group A vs Group B pts (mean relative impact ⫺1.57 ⫾ 0.63 mol/L; p⫽0.02). This decrease in PAGG was independent of IRB dose and BP control. In contrast, Group B pts treated with IRB tended to have greater reduction in E-selectin (⫺7.72 ⫾ 4.10 ng/dl; p⫽0.08); no differential effect on the changes in other inflammatory marker concentrations was noted. There was a greater reduction in TRA-induced PAGG with IRB 300 mg in hyperlipidemic pts (⫺0.67 ⫾ 0.31; p⫽0.05). Conclusion: Our findings suggest a possible impact of ASCVD and hyperlipidemia on the effects of IRB therapy on platelet aggregability and markers of inflammation in hypertensive patients. IRB therapy was associated with greater reduction of PAGG in patients without ASCVD, and of E-selectin concentration in patients with ASCVD. Greater reduction of PAGG in patients with hyperlipidemia may suggest a synergistic effect of IRB and statin therapies. Key Words: Cardiovascular Disease, Angiotensin-Receptor Blocker, Platelet Aggregation
P-228 EQUIVALENT BLOOD PRESSURE REDUCTION WITH ANGIOTENSIN II RECEPTOR ANTAGONIST BASED THERAPY COMPARED WITH A CALCIUM CHANNEL BLOCKER IN MILD-TO-MODERATE HYPERTENSIVE PATIENTS OF AFRICAN ORIGIN Elena N Libhaber, Carlos D Libhaber, Geoffrey P Candy, Karen Sliwa, Ntombi Hlatshwayo, Singh Kavier, Woodiwiss Angela, Norton R Gavin, Essop R Mohammed, Sareli Pinchas. Cardiology, Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa; Nuclear Medicine, Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa; Physiology, University of the Witwatersrand, Johannesburg, South Africa. In the initiation of antihypertensive therapy in patients of African ancestry, calcium channel blockers (CCB) are superior to angiotensin-converting enzyme inhibitors (Sareli et al, Arch Intern Med. 2001;161:965–971). The aim of the study was to evaluate wether CCB agents are superior to other agents that target the renin-angiotensin system (such as angiotensin II receptor blockers [ARB]), when initiating therapy in this ethnic group. Patients of African ancestry with mild-to-moderate hypertension defined as mean daytime ambulatory diastolic BP (DADBP) ⱖ90 mm Hg and ⱕ110 mm Hg (n⫽125, age 50 ⫾ 9, 58% female) were randomized to receive open-label losartan 50 mg or amlodipine 5 mg following a two week run-in placebo phase. If DADBP at 1 month was ⱖ 90 mm Hg, hydrochlorothiazide (HCTZ) was added to those patients receiving the ARB or the dose of amlodipine was increased to 10 mg. If DADBP at 2 month was ⱖ 90 mm Hg, the dose of the ARB was increased to 100 mg and HCTZ to 25 mg and 12.5 mg HCTZ was administered to the amlodipine treated group. Patients were followed for 6 months. There were no differences in baseline characteristics between the two treatment groups. ABP values at 6 months of therapy were similar between the two groups (Table). The initiation of antihypertensive therapy with an ARB is equally as effective at reducing BP values as a CCB in subjects of African ancestry.
AJH–May 2004 –VOL. 17, NO. 5, PART 2
ABP at Baseline and 6 months after therapy SBP/DBP (mmHg) Amlodipine/HCTZ 24-Hour Daytime Nighttime ARB /HCTZ 24-Hour Daytime Nighttime
Baseline N ⫽ 45 145 ⫾ 10/94 ⫾ 5 151 ⫾ 9/99 ⫾ 4 141 ⫾ 12/89 ⫾ 7 N ⫽ 38 145 ⫾ 13/93 ⫾ 6 150 ⫾ 12/97 ⫾ 5 142 ⫾ 16/89 ⫾ 9
6 months N ⫽ 45 124 ⫾ 9/80 ⫾ 6* 127 ⫾ 9/84 ⫾ 6* 121 ⫾ 11/76 ⫾ 7* N ⫽ 38 126 ⫾ 16/80 ⫾ 8* 129 ⫾ 16/84 ⫾ 8* 123 ⫾ 18/75 ⫾ 9*
* p ⬍ 0.0001 (baseline-6months)
Key Words: Antihypertensive Therapy, African Origin, Ambulatory Blood Pressure
P-229 ASSOCIATION OF BP CONTROL AND FREQUENCY OF MORTALITY AND CV MORBIDITY IN HYPERTENSIVE PATIENTS WITH CAD: THE INTERNATIONAL VERAPAMIL SR-TRANDOLAPRIL STUDY Giuseppe Mancia, Rhonda M. Cooper-DeHoff, Ann C. Hewkin, Stuart R. Kupfer, Carl J. Pepine. University of Milan-Bicocca, Milan, Italy; University of Florida, Gainesville, FL; Abbott Laboratories, Chicago, IL. Hypertension is generally considered a risk factor for CV disease; however, limited data are available on the impact of BP reduction on CV outcomes in the hypertensive, CAD population. We evaluated the effects of verapamil SR-based (Ve) and atenolol-based (At) strategies on BP control and relationship to CV outcomes. In the prospective, randomized INternational VErapamil SR/trandolapril STudy (INVEST), 22,576 patients with hypertension and CAD were assigned to Ve or At strategies and followed for 2.7 years (mean). Dose titration and additional drugs (trandolapril and/or HCTZ) were recommended to achieve JNC VI BP targets (⬍140/⬍90 mmHg or ⬍130/⬍85 mmHg in patients with diabetes or renal impairment). The primary outcome (PO) was time to first occurrence of death (all cause), nonfatal MI or nonfatal stroke. At 2 years, the Ve and At strategies had comparable BP control (71.7 vs 70.7% for BP ⬍140/⬍90 mmHg, P⫽0.18), systolic BP reduction (18.7 vs 19.0 mmHg, P⫽0.41) and number of antihypertensive drugs (2.6 mean for both). Incidences of PO, death, MI, and stroke were similar between strategies. In all patients, mean systolic BP ⬎140 mmHg during treatment was associated with increased frequency for the PO (figure). In patients who had not achieved BP control at 6 months, the subsequent frequency of the PO was higher compared with patients who had achieved BP control at 6 months (10.3 vs 6.9%, P⬍0.001). A verapamil SR-based or atenolol-based strategy results in equivalent BP control and CV outcomes in hypertensive patients with CAD. Increased systolic BP is associated with increased frequency of adverse CV outcomes in this population.
Key Words: Blood Pressure Control, Verapamil, Invest
POSTERS: Antihypertensive Drugs
Methods: This randomized, double-blind, placebo-controlled crossover study was performed in 18 non-smokers with Stage I hypertension (10 pts w/o ASCVD [Group A; 60% males; 50% whites]; 8 pts w/ASCVD [Group B; 63% males; 50% white]). Nine pts had hyperlipidemia (8 treated with statins). Patients received IRB or placebo for 6 weeks each (the IRB dose was uptitrated from 150 mg to 300 mg after 3 wks), with a 4-wk wash-out. No antiplatelet, or antidepressant agents, or NSAID were permitted. PAGG was tested with thrombin-receptor agonist (TRA) and adenosin-diphosphate (ADP). Plasma concentration of CRP, IL-6, P-and E-selectins were obtained at baseline and at the end of each treatment period. Results: IRB treatment decreased SBP (mean ⫾ SD mm Hg; from 146.4 ⫾ 12.4 to 140.7 ⫾ 10.3; p⬍0.05). There was a greater impact of IRB on reduction of ADP-induced PAGG in Group A vs Group B pts (mean relative impact ⫺1.57 ⫾ 0.63 mol/L; p⫽0.02). This decrease in PAGG was independent of IRB dose and BP control. In contrast, Group B pts treated with IRB tended to have greater reduction in E-selectin (⫺7.72 ⫾ 4.10 ng/dl; p⫽0.08); no differential effect on the changes in other inflammatory marker concentrations was noted. There was a greater reduction in TRA-induced PAGG with IRB 300 mg in hyperlipidemic pts (⫺0.67 ⫾ 0.31; p⫽0.05). Conclusion: Our findings suggest a possible impact of ASCVD and hyperlipidemia on the effects of IRB therapy on platelet aggregability and markers of inflammation in hypertensive patients. IRB therapy was associated with greater reduction of PAGG in patients without ASCVD, and of E-selectin concentration in patients with ASCVD. Greater reduction of PAGG in patients with hyperlipidemia may suggest a synergistic effect of IRB and statin therapies. Key Words: Cardiovascular Disease, Angiotensin-Receptor Blocker, Platelet Aggregation
P-228 EQUIVALENT BLOOD PRESSURE REDUCTION WITH ANGIOTENSIN II RECEPTOR ANTAGONIST BASED THERAPY COMPARED WITH A CALCIUM CHANNEL BLOCKER IN MILD-TO-MODERATE HYPERTENSIVE PATIENTS OF AFRICAN ORIGIN Elena N Libhaber, Carlos D Libhaber, Geoffrey P Candy, Karen Sliwa, Ntombi Hlatshwayo, Singh Kavier, Woodiwiss Angela, Norton R Gavin, Essop R Mohammed, Sareli Pinchas. Cardiology, Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa; Nuclear Medicine, Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa; Physiology, University of the Witwatersrand, Johannesburg, South Africa. In the initiation of antihypertensive therapy in patients of African ancestry, calcium channel blockers (CCB) are superior to angiotensin-converting enzyme inhibitors (Sareli et al, Arch Intern Med. 2001;161:965–971). The aim of the study was to evaluate wether CCB agents are superior to other agents that target the renin-angiotensin system (such as angiotensin II receptor blockers [ARB]), when initiating therapy in this ethnic group. Patients of African ancestry with mild-to-moderate hypertension defined as mean daytime ambulatory diastolic BP (DADBP) ⱖ90 mm Hg and ⱕ110 mm Hg (n⫽125, age 50 ⫾ 9, 58% female) were randomized to receive open-label losartan 50 mg or amlodipine 5 mg following a two week run-in placebo phase. If DADBP at 1 month was ⱖ 90 mm Hg, hydrochlorothiazide (HCTZ) was added to those patients receiving the ARB or the dose of amlodipine was increased to 10 mg. If DADBP at 2 month was ⱖ 90 mm Hg, the dose of the ARB was increased to 100 mg and HCTZ to 25 mg and 12.5 mg HCTZ was administered to the amlodipine treated group. Patients were followed for 6 months. There were no differences in baseline characteristics between the two treatment groups. ABP values at 6 months of therapy were similar between the two groups (Table). The initiation of antihypertensive therapy with an ARB is equally as effective at reducing BP values as a CCB in subjects of African ancestry.
AJH–May 2004 –VOL. 17, NO. 5, PART 2
ABP at Baseline and 6 months after therapy SBP/DBP (mmHg) Amlodipine/HCTZ 24-Hour Daytime Nighttime ARB /HCTZ 24-Hour Daytime Nighttime
Baseline N ⫽ 45 145 ⫾ 10/94 ⫾ 5 151 ⫾ 9/99 ⫾ 4 141 ⫾ 12/89 ⫾ 7 N ⫽ 38 145 ⫾ 13/93 ⫾ 6 150 ⫾ 12/97 ⫾ 5 142 ⫾ 16/89 ⫾ 9
6 months N ⫽ 45 124 ⫾ 9/80 ⫾ 6* 127 ⫾ 9/84 ⫾ 6* 121 ⫾ 11/76 ⫾ 7* N ⫽ 38 126 ⫾ 16/80 ⫾ 8* 129 ⫾ 16/84 ⫾ 8* 123 ⫾ 18/75 ⫾ 9*
* p ⬍ 0.0001 (baseline-6months)
Key Words: Antihypertensive Therapy, African Origin, Ambulatory Blood Pressure
P-229 ASSOCIATION OF BP CONTROL AND FREQUENCY OF MORTALITY AND CV MORBIDITY IN HYPERTENSIVE PATIENTS WITH CAD: THE INTERNATIONAL VERAPAMIL SR-TRANDOLAPRIL STUDY Giuseppe Mancia, Rhonda M. Cooper-DeHoff, Ann C. Hewkin, Stuart R. Kupfer, Carl J. Pepine. University of Milan-Bicocca, Milan, Italy; University of Florida, Gainesville, FL; Abbott Laboratories, Chicago, IL. Hypertension is generally considered a risk factor for CV disease; however, limited data are available on the impact of BP reduction on CV outcomes in the hypertensive, CAD population. We evaluated the effects of verapamil SR-based (Ve) and atenolol-based (At) strategies on BP control and relationship to CV outcomes. In the prospective, randomized INternational VErapamil SR/trandolapril STudy (INVEST), 22,576 patients with hypertension and CAD were assigned to Ve or At strategies and followed for 2.7 years (mean). Dose titration and additional drugs (trandolapril and/or HCTZ) were recommended to achieve JNC VI BP targets (⬍140/⬍90 mmHg or ⬍130/⬍85 mmHg in patients with diabetes or renal impairment). The primary outcome (PO) was time to first occurrence of death (all cause), nonfatal MI or nonfatal stroke. At 2 years, the Ve and At strategies had comparable BP control (71.7 vs 70.7% for BP ⬍140/⬍90 mmHg, P⫽0.18), systolic BP reduction (18.7 vs 19.0 mmHg, P⫽0.41) and number of antihypertensive drugs (2.6 mean for both). Incidences of PO, death, MI, and stroke were similar between strategies. In all patients, mean systolic BP ⬎140 mmHg during treatment was associated with increased frequency for the PO (figure). In patients who had not achieved BP control at 6 months, the subsequent frequency of the PO was higher compared with patients who had achieved BP control at 6 months (10.3 vs 6.9%, P⬍0.001). A verapamil SR-based or atenolol-based strategy results in equivalent BP control and CV outcomes in hypertensive patients with CAD. Increased systolic BP is associated with increased frequency of adverse CV outcomes in this population.
Key Words: Blood Pressure Control, Verapamil, Invest