Potential impact of the 2017 ACC/AHA guideline on high blood pressure in normotensive patients with stable coronary artery disease: insights from the CLARIFY registry

Aims: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline on high blood pressure (BP) lowered the threshold defining hypertension and BP target in high-risk patients to 130/80 mmHg. Patients with coronary artery disease and systolic BP 130-139 mmHg or diastolic BP 80-89 mmHg should now receive medication to achieve this target. We aimed to investigate the relationship between BP and cardiovascular events in 'real-life' patients with coronary artery disease considered as having normal BP until the recent guideline. Methods and results: Data from 5956 patients with stable coronary artery disease, no history of hypertension or heart failure, and average BP <140/90 mmHg, enrolled in the CLARIFY registry (November 2009 to June 2010), were analysed. In a multivariable-adjusted Cox proportional hazards model, after a median follow-up of 5.0 years, diastolic BP 80-89 mmHg, but not systolic BP 130-139 mmHg, was associated with increased risk of the primary endpoint, a composite of cardiovascular death, myocardial infarction, or stroke (hazard ratio 2.15, 95% confidence interval 1.22-3.81 vs. 70-79 mmHg and 1.12, 0.64-1.97 vs. 120-129 mmHg). No significant increase in risk for the primary endpoint was observed for systolic BP <120 mmHg or diastolic BP <70 mmHg. Conclusion: In patients with stable coronary artery disease defined as having normal BP according to the 140/90 mmHg threshold, diastolic BP 80-89 mmHg was associated with increased cardiovascular risk, whereas systolic BP 130-139 mmHg was not, supporting the lower diastolic but not the lower systolic BP hypertension-defining threshold and treatment target in coronary artery disease. ClinicalTrials identifier: ISRCTN43070564

Prevalence of diabetic and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities

Background: In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods: CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia and Africa in 2009-2010, and followed-up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia, or prior revascularisation procedure. Results: Among 32,694patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to approximately 60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome(cardiovascular death, myocardial infarction or stroke)with an adjusted hazard ratio of1.28(95% CI 1.18-1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion: In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes

B-blockers, calcium antagonists, and mortality in stable coronary artery disease: An international cohort study

Aims: The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. Methods and results We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. Conclusion In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI

Rationale, design, and baseline characteristics of the CLARIFY registry of outpatients with stable coronary artery disease

Background: Despite major advances in prevention and treatment, coronary artery disease (CAD) remains the leading cause of death worldwide. Whereas many sources of data are available on the epidemiology of acute coronary syndromes, fewer datasets reflect the contemporary management and outcomes of stable CAD patients. Hypothesis: A worldwide contemporary registry would improve our knowledge about stable CAD. The main objectives are to describe the demographics, clinical profile, contemporary management and outcomes of outpatients with stable CAD; to identify gaps between evidence and treatment; and to investigate long-term prognostic determinants. Methods: CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an ongoing international observational longitudinal registry. Stable CAD patients from 45 countries in Europe, Asia, America, Middle East, Australia and Africa were enrolled between November 2009 and June 2010. The inclusion criteria were previous myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia or prior revascularization procedure. The main exclusion criteria were serious non-cardiovascular disease, conditions interfering with life expectancy or severe other cardiovascular disease (including advanced heart failure). Follow-up visits were planned annually for up to 5 years, interspersed with 6-month telephone calls. Results: Of the 32,703 patients enrolled, most (77.6%) were male, age (mean ± SD) was 64.2 ± 10.5 years, and 71.0% were receiving treatment for hypertension; mean ± SD resting heart rate was 68.2 ± 10.6 bpm. Patients were enrolled based on a history of myocardial infarction >3 months earlier (57.7%), having at least one stenosis >50% on coronary angiography (61.1%), proven symptomatic myocardial ischemia on non-invasive testing (23.1%), or history of percutaneous coronary intervention or coronary artery bypass graft (69.8%). Baseline characteristics were similar across the four subgroups identified by the four inclusion criteria. Conclusion: CLARIFY will provide a useful resource for understanding the current epidemiology of stable CAD

Use of risk scores to identify lower and higher risk subsets among COMPASS-eligible patients with chronic coronary syndromes. Insights from the CLARIFY Registry

Background: The COMPASS trial showed a reduction of ischemic events with low‐dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding. Hypothesis: The CHA2DS2VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade‐off between ischemic and bleeding events, among COMPASS‐eligible patients. Methods: We identified the COMPASS‐eligible population within the CLARIFY registry (>30.000 patients with CCS). High‐bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0–1) or high (≥ 2) CHA2DS2VaSc; low (0–12) or intermediate (13–19) REACH RIS, and low (0–6) or intermediate (7–10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion). Results: The COMPASS‐eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1–2.5) and 0.5 (0.4–0.6) per 100 patient‐years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6–3.4]) with similar bleeding risk (0.5 [0.4–0.7]) as the overall population. Patients with low CHA2DS2VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3–1.3]) with similar bleeding risk (0.5 [0.2–1.1]). Conclusions: Intermediate REACH RIS identified potential optimal candidates for adjunction of low‐dose rivaroxaban while patients with low CHA2DS2VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding

Relationship between physical activity and long-term outcomes in patients with stable coronary artery disease

AIMS To ascertain the relationship between level of physical activity and outcomes and to discriminate the determinants of physical activity performance or avoidance. METHODS CLARIFY is an international prospective registry of 32370 consecutive outpatients with stable coronary artery disease who were followed for up to 5 years. Patients were grouped according to the level and frequency of physical activity: i) sedentary (n=5223; 16.1%); ii) only light physical activity most weeks (light; n=16634; 51.4%); iii) vigorous physical activity once or twice per week (vigorous ≤2×; n=5427; 16.8%); iv) vigorous physical activity three or more times per week (vigorous >2×; n=5086; 15.7%). The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. RESULTS Patients performing vigorous physical activity ≤2× had the lowest risk of the primary outcome (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.93; P = .0031) taking the light group as reference. Engaging in more frequent exercise did not result in further outcome benefit. All-cause death, cardiovascular death, and stroke occurred less frequently in patients performing vigorous physical activity ≤2×. However, the rate of myocardial infarction was comparable between the four physical activity groups. Female sex, peripheral artery disease, diabetes, previous myocardial infarction or stroke, pulmonary disease, and body mass index all emerged as independent predictors of lower physical activity. CONCLUSION Vigorous physical activity once or twice per week was associated with superior cardiac outcomes compared to patients performing no or a low level of physical activity in outpatients with stable coronary artery disease