Atenolol-based Strategies Research Articles

Effects of verapamil SR and atenolol on 24-hour blood pressure and heart rate in hypertension patients with coronary artery disease: an international verapamil SR-trandolapril ambulatory monitoring substudy.

Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.Trial RegistrationClinicaltrials.gov; NCT00133692

Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril STudy (INVEST) analysis

The purpose of this study was to assess the relationship between pulse pressure (PP) and cardiovascular outcomes in a large, elderly, coronary artery disease (CAD) population with hypertension, and compare the predictive power of PP with other blood pressure measures. In INternational VErapamil-trandolapril STudy, 22,576 CAD patients with hypertension (mean age 66 years) were randomized to verapamil-SR or atenolol-based strategies and followed for 2.7 years (mean). Primary outcome (PO) was time to first occurrence of death (all-cause), non-fatal myocardial infarction (MI), or non-fatal stroke. Mean follow-up PP was summarized by 5 mmHg subgroups for association with incidence of PO. Stepwise Cox proportional hazards models were used to estimate adjusted relative hazard ratios (HR) for the risk of PO with follow-up PP as a continuous variable, with linear and quadratic terms. Similar models were constructed for follow-up systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP). A -2 log-likelihood statistic was used to assess the predictive power of PP compared with SBP, DBP, and MAP. For follow-up PP, the incidence and adjusted HR for the PO formed a J- or U-shaped curve. After adjusting for baseline covariates, both linear and quadratic terms for PP were significant (P < 0.0001 for both), with a nadir of 54 mmHg (bootstrapping 95% CI 42-60 mmHg). Similar quadratic relationships were found between PP and all-cause mortality or MI; the relationship between PP and stroke was linear. Pulse pressure was a predictor of PO even after including SBP (P = 0.007 linear term) or DBP (P < 0.0001 for both linear and quadratic terms) or MAP (P < 0.01 for both liner and quadratic terms) in the model. Using -2 log-likelihood differences, SBP (-2 log-likelihood difference 77.1 vs. 7.3 for PP), DBP (-2 log-likelihood difference 138.5 vs. 44.6 for PP), and MAP (-2 log-likelihood difference 125.0 vs. 13.4 for PP) were stronger predictors of PO than PP. In CAD patients with hypertension, PP (on anti-hypertensive treatment) is a weaker predictor of cardiovascular outcomes than SBP, DBP, or MAP.

Verapamil-sustained release–based treatment strategy is equivalent to atenolol-based treatment strategy at reducing cardiovascular events in patients with prior myocardial infarction: An INternational VErapamil SR-Trandolapril (INVEST) substudy

In patients with prior myocardial infarction (MI), beta-blockers reduce mortality by 23% to 40%. However, despite this favorable effect, adverse effects limit compliance to this medication. The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI. We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Trandolapril (INVEST) substudy randomized to verapamil-sustained release (SR)- or atenolol-based strategies. Primary outcome was time to first occurrence of death (all-cause), nonfatal MI, or nonfatal stroke. Secondary outcomes included death, total MI (fatal and nonfatal), and total stroke (fatal and nonfatal) considered separately. During the 2.8 +/- 1.0 years of follow-up, patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control, and the incidence of the primary outcome was equivalent. There was no difference between the 2 strategies for the outcomes of either death or total MI. However, more patients reported excellent/good well-being (82.3% vs 78.0%, P = .02) at 24 months with a trend toward less incidence of angina pectoris (12.0% vs 14.3%, adjusted P = .07), nonfatal stroke (1.4% vs 2.0%; P = .06), and total stroke (2.0% vs 2.5%, P = .18) in the verapamil-SR-based strategy group. In hypertensive patients with prior MI, a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events, with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group.

High resting heart rate: a cardiovascular risk factor or a marker of risk?

We read with interest the work of Kolloch et al. 1 about the relationship between resting heart rate (RHR) and adverse events in patients with hypertension and coronary artery disease from the population of the INternational VErapamil-SR/trandolapril STudy (INVEST study). This study reported that higher baseline and follow-up RHR were associated with increased adverse outcome risks. Taking into account that this study showed that, despite the atenolol-based strategy …

Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?

Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. 862 sites in 14 countries. 22 576 patients with hypertension and CAD. Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. This is a post hoc analysis of hypertensive patients with CAD. The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.

Depressive Symptoms in Coronary Artery Disease Patients After Hypertension Treatment

Depression is highly prevalent and frequently recurs in patients with coronary artery disease (CAD) and hypertension. Certain medications used to treat hypertension are alleged to be associated with higher risk of depression. To compare depressive symptoms before and during treatment with 2 equivalent hypertension treatment strategies in patients with CAD stratified according to a self-reported history of physician-diagnosed depression. Patients enrolled in a randomized hypertension treatment study were mailed baseline and one year follow-up surveys and stratified according to a self-reported history of depression. Patients (N = 1152) were 50 years old or older with hypertension and clinically stable CAD. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D). High risk of depression was defined as a history of physician-diagnosed depression reported by patients on the baseline survey. Depressive symptoms were compared for verapamil sustained-release (SR)- and atenolol-based hypertension treatment. Among patients with a previous history of depression, depressive symptoms improved over the one year follow-up period for patients assigned to both treatment regimens. Depressive symptoms improved for patients with no depression history in the verapamil SR group (p < 0.001) and were unchanged in the atenolol group (p = 0.52). Patients assigned to the atenolol-based strategy without prior history of depression were more likely to worsen 5 or more points on the CES-D. When antihypertensive treatment options are clinically equivalent, prescribers may first consider using a verapamil SR-based strategy, especially in patients with CAD who have no history of depression.

Predictors of Adverse Outcome Among Patients With Hypertension and Coronary Artery Disease

We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Verapamil- and atenolol-based strategies are equally effective in black patients with hypertension and coronary artery disease: A subanalysis of the international verapamil SR-trandolapril study (INVEST)

This INVEST subanalysis investigated the antihypertensive and cardiovascular effects of verapamil SR (Ve) or atenolol (At) strategies in Black patients with hypertension (HTN) and coronary artery disease (CAD). INVEST randomized 22,576 HTN CAD patients to a Ve- or At-based strategy. Dose titration and additional of trandolapril and/or HCTZ were recommended to achieve JNC VI BP targets. Overall incidence of the primary outcome (death, nonfatal MI, or nonfatal stroke [PO]) was equivalent between strategies. Black patients comprised 13% of the study and had a PO rate of 11.6% in both strategies (HR = 0.99; 95% CI 0.80, 1.22), compared to a PO rate of 12.1% for Caucasian patients in both strategies. Baseline characteristics, rates of death, nonfatal MI, nonfatal stroke and BP control were similar for Black patients in the two strategies, except that 24 month BP control (<140/90 mmHg) was significantly better in the Ve group (table). Greater than 60% of Black patients received 3 or more antihypertension drugs at month 24. INVEST Black Patients # p-values from one-way ANOVA for continuous variables, chi-square test for categorical variables, log- rank test for outcomes INVEST Black Patients # p-values from one-way ANOVA for continuous variables, chi-square test for categorical variables, log- rank test for outcomes In conclusion, verapamil- and atenolol-based multidrug strategies are equally effective in Black patients with hypertension and CAD when BP control, cardiovascular morbidity and mortality endpoints are considered.

Incidence of MI is equivalent with verapamil SR-based and atenolol-based strategies in patients with hypertension and CAD: the international verapamil SR-trandolapril study

P-423 Key Words: Myocardial Infarction, Verapamil, Invest

Association of BP control and frequency of mortality and CV morbidity in hypertensive patients with CAD: the international verapamil SR-trandolapril study

P-229 Key Words: Blood Pressure Control, Verapamil, Invest