- Email: [email protected]
Ivabradine Improves Symptoms and Quality of Life in Chronic Systolic Heart Failure Patients With Different Baseline Symptom Severity
S46 Journal of Cardiac Failure Vol. 21 No. 8S August 2015
Table 1. Absolute percent changes in patients in the 4 NYHA groups treated with ivabradine for 4 months
D
Baseline-4
months
Heart rate (bpm) Patients in this NYHA class Patients with signs of decompensation Patients with BNP O 400 pg/ml EQ-5D index score (QoL) Patients with treatment responsea a
1 (n 5 184)
II (n 5 981)
III (n 5 715)
-20 612 +14%
-17 6 12 +9%
-19 613 -22%
IV (n 5 41) -21 613 -1%
-2%
-9%
-32%
-30%
-6%
-16%
-37%
-24%
+0.10 91%
+0.13 87%
+0.20 91%
+0.24 92%
Defined as HR ! 70 bpm or HR reduction of $ 10 bpm at study end.
ivabradine treatment (87-92%; Table 1). Conclusions: Ivabradine was effective in reducing heart rate and symptoms of CHF in patients with all grades of baseline symptom severity. Ivabradine also reduced BNP, improved QoL in all NYHA groups, was well-tolerated, and had high rates of treatment response. Effects were more pronounced in patients with higher NYHA classes. Figure 1.
090
089 Ivabradine Improves Symptoms and Quality of Life in Chronic Systolic Heart Failure Patients With Different Baseline Symptom Severity Christian Zugck1, Peter Martinka2, Georg St€ockl2; 1Internistische Gemeinschaftspraxis im Steiner Thor, Straubing, Germany; 2Servier Deutschland GmbH, M€unchen, Germany Introduction: The prospective, open-label, multicenter INTENSIfY study evaluated the effectiveness, tolerability, and effect on quality of life (QoL) of ivabradine treatment over a 4-month period in patients with chronic systolic heart failure (CHF). We performed a subgroup analysis to characterize the effectiveness and safety of ivabradine in addition to standard heart failure medication in patients with different severity of CHF symptoms. Methods: Resting heart rate (HR), heart failure symptoms (NYHA class, signs of decompensation), and concomitant medication were documented in ambulatory CHF patients. BNP measurements were tracked in subset of patients. Treatment with flexible doses of ivabradine twice daily was initiated for 4 months; dose adjustment was possible after 1 month. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis of the results was performed for four subgroups defined by NYHA class at baseline (NYHA I-IV). Results: In total, 1956 patients (intention to treat, mean age 67.2611.7 years, 56% male) were analyzed. Etiology was ischemic for 62%; diagnosis had been known for more than 6 months for 85% of all patients. Overall, 78% received beta blockers: 33% metoprolol, mean daily dose (mdd) 102.9 mg; 28% bisoprolol, mdd 6.2 mg; 9% nebivolol, mdd 5.4 mg; and 7% carvedilol, mdd 27.1 mg). Other concomitant medication included ACEI/ARB (83%), diuretics (61%), aldosterone antagonists (18%), cardiac glycosides (8%), aspirin (58%), and statins (56%). After 4 months of ivabradine treatment (overall mdd 12.44 mg), patients had decreases in heart rate (17-21%) and increases in QoL scores (0.1-0.24), and most responded to
Effect of Comorbidities and Risk Factors on Outcomes and Ivabradine’s Effects in Patients With Chronic Systolic Heart Failure in the SHIFT Trial Michael B€ohm1, Jeffrey S. Borer2, Ian Ford3, Michel Komajda4, Michele Robertson3, Luigi Tavazzi5, Karl Swedberg6; 1Universit€atskliniken des Saarlandes, Homburg/ Saar, Germany; 2State University of New York Downstate Medical Center, New York, NY; 3University of Glasgow, Glasgow, United Kingdom; 4University Pierre et Marie Curie Paris VI, Paris, France; 5Maria Cecilia Hospital, Cotignola, Italy; 6 University of Gothenburg, G€oteborg, Sweden Background: A wide range of cardiovascular and non-cardiac comorbidities may complicate heart failure (HF), increasing morbidity and mortality risk. Despite a high prevalence of comorbidities, there is limited evidence on the effects of multiple comorbidities on treatment outcomes in patients with HF. The SHIFT study showed that ivabradine significantly improved major HF outcomes in patients with HF receiving guidelines-based background HF treatment with sinus rhythm heart rate $70 bpm and left ventricular ejection fraction #35%. Methods: We explored the relative impact of multi-morbidities on outcomes and their potential impact on ivabradine’s effect in SHIFT HF patients. Results: The most frequent preexisting comorbidities in the 6505 patients (3241 on ivabradine; 3264 on placebo) were history of hypertension (66%), myocardial infarction (56%), diabetes mellitus (30%), renal dysfunction (estimated GFR !60 mL/min/1.73 m2; 26%), chronic obstructive pulmonary disease (11%), anemia (hemoglobin #11.5 g/dL; 6%), history of stroke (7%), and peripheral artery disease (6%); 10% of patients did not have any of these comorbidities, 53% had $2, and 37% had $3. Multimorbidity was associated with higher risk of outcomes: the greater the number of comorbidities, the higher the risk. With ivabradine, there was a reduction in the primary outcome of cardiovascular death or hospitalization for HF and in other HF-related outcomes (Table 1). Conclusions: Comorbidities increased events in patients with chronic HF, with multi-morbidity increasing the likelihood of an adverse outcome. The number of morbidities did not interfere with the effects of ivabradine.
Table 1. Adjusted hazard ratios (95% confidence intervals) of the risk of heart failure-related outcomes in relation to comorbidities
Number of Comorbidities
Primary end point Heart failure hospitalization Heart failure mortality Total hospitalizations
No Comorbidities
1-2 Comorbidities
# 3 Comorbidities
Interaction P-value
0.74 (0.54,1.01) P50.028 0.64 (0.44, 0.94) P50.022 0.75 (0.37,1.52) P50.42 0.79 (0.60,1.04) P50.086
0.81 (0.70, 0.93) P50.0027 0.72 (0.61, 0.86) P50.0002 0.86 (0.60, 1.24) P50.43 0.87 (0.77, 0.97) P50.013
0.88 (0.76, 1.02) P50.082 0.81 (0.69. 0.96) P50.017 0.67 (0.46, 0.98) P50.038 0.95 (0.85,1.06) P50.37
0.18 0.13 0.54 0.13
Table 1. Absolute percent changes in patients in the 4 NYHA groups treated with ivabradine for 4 months
D
Baseline-4
months
Heart rate (bpm) Patients in this NYHA class Patients with signs of decompensation Patients with BNP O 400 pg/ml EQ-5D index score (QoL) Patients with treatment responsea a
1 (n 5 184)
II (n 5 981)
III (n 5 715)
-20 612 +14%
-17 6 12 +9%
-19 613 -22%
IV (n 5 41) -21 613 -1%
-2%
-9%
-32%
-30%
-6%
-16%
-37%
-24%
+0.10 91%
+0.13 87%
+0.20 91%
+0.24 92%
Defined as HR ! 70 bpm or HR reduction of $ 10 bpm at study end.
ivabradine treatment (87-92%; Table 1). Conclusions: Ivabradine was effective in reducing heart rate and symptoms of CHF in patients with all grades of baseline symptom severity. Ivabradine also reduced BNP, improved QoL in all NYHA groups, was well-tolerated, and had high rates of treatment response. Effects were more pronounced in patients with higher NYHA classes. Figure 1.
090
089 Ivabradine Improves Symptoms and Quality of Life in Chronic Systolic Heart Failure Patients With Different Baseline Symptom Severity Christian Zugck1, Peter Martinka2, Georg St€ockl2; 1Internistische Gemeinschaftspraxis im Steiner Thor, Straubing, Germany; 2Servier Deutschland GmbH, M€unchen, Germany Introduction: The prospective, open-label, multicenter INTENSIfY study evaluated the effectiveness, tolerability, and effect on quality of life (QoL) of ivabradine treatment over a 4-month period in patients with chronic systolic heart failure (CHF). We performed a subgroup analysis to characterize the effectiveness and safety of ivabradine in addition to standard heart failure medication in patients with different severity of CHF symptoms. Methods: Resting heart rate (HR), heart failure symptoms (NYHA class, signs of decompensation), and concomitant medication were documented in ambulatory CHF patients. BNP measurements were tracked in subset of patients. Treatment with flexible doses of ivabradine twice daily was initiated for 4 months; dose adjustment was possible after 1 month. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis of the results was performed for four subgroups defined by NYHA class at baseline (NYHA I-IV). Results: In total, 1956 patients (intention to treat, mean age 67.2611.7 years, 56% male) were analyzed. Etiology was ischemic for 62%; diagnosis had been known for more than 6 months for 85% of all patients. Overall, 78% received beta blockers: 33% metoprolol, mean daily dose (mdd) 102.9 mg; 28% bisoprolol, mdd 6.2 mg; 9% nebivolol, mdd 5.4 mg; and 7% carvedilol, mdd 27.1 mg). Other concomitant medication included ACEI/ARB (83%), diuretics (61%), aldosterone antagonists (18%), cardiac glycosides (8%), aspirin (58%), and statins (56%). After 4 months of ivabradine treatment (overall mdd 12.44 mg), patients had decreases in heart rate (17-21%) and increases in QoL scores (0.1-0.24), and most responded to
Effect of Comorbidities and Risk Factors on Outcomes and Ivabradine’s Effects in Patients With Chronic Systolic Heart Failure in the SHIFT Trial Michael B€ohm1, Jeffrey S. Borer2, Ian Ford3, Michel Komajda4, Michele Robertson3, Luigi Tavazzi5, Karl Swedberg6; 1Universit€atskliniken des Saarlandes, Homburg/ Saar, Germany; 2State University of New York Downstate Medical Center, New York, NY; 3University of Glasgow, Glasgow, United Kingdom; 4University Pierre et Marie Curie Paris VI, Paris, France; 5Maria Cecilia Hospital, Cotignola, Italy; 6 University of Gothenburg, G€oteborg, Sweden Background: A wide range of cardiovascular and non-cardiac comorbidities may complicate heart failure (HF), increasing morbidity and mortality risk. Despite a high prevalence of comorbidities, there is limited evidence on the effects of multiple comorbidities on treatment outcomes in patients with HF. The SHIFT study showed that ivabradine significantly improved major HF outcomes in patients with HF receiving guidelines-based background HF treatment with sinus rhythm heart rate $70 bpm and left ventricular ejection fraction #35%. Methods: We explored the relative impact of multi-morbidities on outcomes and their potential impact on ivabradine’s effect in SHIFT HF patients. Results: The most frequent preexisting comorbidities in the 6505 patients (3241 on ivabradine; 3264 on placebo) were history of hypertension (66%), myocardial infarction (56%), diabetes mellitus (30%), renal dysfunction (estimated GFR !60 mL/min/1.73 m2; 26%), chronic obstructive pulmonary disease (11%), anemia (hemoglobin #11.5 g/dL; 6%), history of stroke (7%), and peripheral artery disease (6%); 10% of patients did not have any of these comorbidities, 53% had $2, and 37% had $3. Multimorbidity was associated with higher risk of outcomes: the greater the number of comorbidities, the higher the risk. With ivabradine, there was a reduction in the primary outcome of cardiovascular death or hospitalization for HF and in other HF-related outcomes (Table 1). Conclusions: Comorbidities increased events in patients with chronic HF, with multi-morbidity increasing the likelihood of an adverse outcome. The number of morbidities did not interfere with the effects of ivabradine.
Table 1. Adjusted hazard ratios (95% confidence intervals) of the risk of heart failure-related outcomes in relation to comorbidities
Number of Comorbidities
Primary end point Heart failure hospitalization Heart failure mortality Total hospitalizations
No Comorbidities
1-2 Comorbidities
# 3 Comorbidities
Interaction P-value
0.74 (0.54,1.01) P50.028 0.64 (0.44, 0.94) P50.022 0.75 (0.37,1.52) P50.42 0.79 (0.60,1.04) P50.086
0.81 (0.70, 0.93) P50.0027 0.72 (0.61, 0.86) P50.0002 0.86 (0.60, 1.24) P50.43 0.87 (0.77, 0.97) P50.013
0.88 (0.76, 1.02) P50.082 0.81 (0.69. 0.96) P50.017 0.67 (0.46, 0.98) P50.038 0.95 (0.85,1.06) P50.37
0.18 0.13 0.54 0.13